(Hypertension. 1997;29:105.)
© 1997 American Heart Association, Inc.
Research Articles (Issue 1, Part 1) |
Pressor Effects of Endogenous Opioid System During Acute Episodes of Blood Pressure Increases in Hypertensive Patients
Istituto di Patologia Speciale Medica e Metodologia Clinica, Ospedale S Orsola (F.F., P.B.); Dipartimento di Farmacologia (S.S.); Servizio di Farmacologia Clinica, Ospedale S Orsola (S.B., R. De I.); and Laboratorio Centralizzato, Ospedale S Orsola (G.G.), Bologna, Italy.
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
To investigate the involvement of endogenous opioids in acute increases in blood pressure and their functional relationship with atrial natriuretic factor and endothelin-1, we assessed plasma levels of ß-endorphin, met-enkephalin, dynorphin B, catecholamines, atrial natriuretic factor, and endothelin-1 before and after administration of the opioid antagonist naloxone hydrochloride (8 mg IV) in 28 hypertensive patients with a stress-induced acute increase in blood pressure. Ten patients with established mild or moderate essential hypertension and 10 normotensive subjects served as control groups. Opioids, atrial natriuretic factor, and endothelin-1 were radioimmunoassayed after chromatographic preextraction; catecholamines were determined by high-performance liquid chromatography with electrochemical detection. Patients with an acute increase in blood pressure (systolic, 203.2±2.2 mm Hg; diastolic, 108.4±1.3) had plasma opioid, catecholamine, and atrial natriuretic factor levels significantly (P<.01) higher than hypertensive control patients (systolic pressure, 176.4±1.0 mm Hg; diastolic, 100.0±1.4), who had a hormonal pattern similar to that of normotensive subjects (systolic pressure, 123.2±1.5 mm Hg; diastolic, 75.0±2.0). Endothelin-1 did not differ in any group. In patients with an acute increase in blood pressure, naloxone significantly (P<.01) reduced blood pressure, heart rate, opioids, catecholamines, and atrial natriuretic factor 10 minutes after administration. Naloxone effects on blood pressure, heart rate, opioids, and catecholamines wore off within 20 minutes. In control groups, naloxone failed to modify any of the considered parameters. Our findings suggest that pressor effects of opioid peptides mediated by the autonomic nervous system during stress-induced acute episodes of blood pressure increase in hypertensive patients.
Key Words: blood pressure • catecholamines • atrial natriuretic factor • endothelin-1 • naloxone
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Endogenous opioid peptides and their receptors are distributed in the periphery (eg, heart,1 blood vessels,2 sympathetic nerves,3 4 and adrenal glands5 ) as well as in the central nervous system,6 7 providing the structural bases for numerous interactions in systemic circulatory regulation. Activation of the opioid peptide system in the periphery has been shown to presynaptically inhibit norepinephrine release from sympathetic nerve terminals,8 with subsequent vasodilation. Intravenous administration of dynorphin9 and ß-endorphin10 produces hypotension in experimental animals and humans. Functional studies have also shown a role of opioid peptides in the central control of BP depending on distinct inhibitory inputs to a pressor area (rostral part of the ventral medulla) and to a depressor area (caudal ventrolateral medulla),11 both regulating sympathoadrenergic activity. Biochemical and pharmacological data suggest the involvement of the central opioid system in the development of spontaneous and experimental hypertension in animals.12
Evidence for a role of the endogenous opioid system in human hypertension is still under scrutiny. Studies in humans with established essential hypertension failed to show any effect on BP of the opioid antagonist naloxone.13 Recently, we have shown that naloxone administration transiently decreased BP in patients with hypertensive crises during acute cerebral ischemia.14 These data suggest that the opioid peptide system may be implicated in the control of the dynamic BP changes frequently observed in patients with essential hypertension. Clinically hypertensive patients are known to be hyperreactive when exposed to stressors15 ; in these patients, the increased cardiovascular response to stress implies an increased sympathoadrenergic activity and suggests impairments in the BP regulatory mechanism.15
In the present study, we investigated whether endogenous opioid peptides play a role in acute BP increase, spontaneously intervening after psychophysical stress, in essential hypertensive patients without signs of organ damage or circulatory failure. We measured plasma concentrations of the three main circulating opioid peptides—ß-endorphin, met-enkephalin, and dynorphin B—and catecholamines before and after naloxone hydrochloride administration. Moreover, we also assessed circulating levels of ANF and ET-1 to evaluate possible functional relationships between endogenous opioids and these vasoactive peptides, which are mainly released in response to acute stress.16 17
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Subjects
A group of 28 patients (20 men aged 54.0±5.5 years and 8 women aged 55.3±6.1 years) with spontaneously intervening acute episodes of BP increases were studied. They were recruited from the emergency ward and the Hypertension Clinic at our institution. On the basis of BP values previously observed in many of these patients attending our Hypertension Clinic and on their clinical history, they had mild or moderate essential hypertension (World Health Organization grades I and II; mean duration of hypertension, 24±4 months), controlled by various combinations of angiotensin-converting enzyme inhibitors, calcium antagonists, and diuretics. In previous clinical controls, the patients were asymptomatic and had systolic BP not above 160 mm Hg and diastolic BP not above 90 mm Hg. The symptoms that brought these patients to medical attention were one or more of the following: dyspnea, headache, dizziness, palpitations, and epistaxis. The delay between the onset of symptoms and our observation ranged from 1 to 3 hours. Patients with pulmonary edema, cerebrovascular accidents, and acute coronary artery diseases were excluded. According to patient reports, the acute increase in BP was apparently related to various physical or psychological stresses, such as excessive food intake, exaggerated physical exercise, work overload, or anxiety. Routine biochemical analyses of blood and urine were normal, and secondary causes of hypertension were excluded. All patients were in sinus rhythm. Six patients presented left ventricular hypertrophy; 8 showed mild impairment in cardiac diastolic function; none had ejection fraction less than 55%, increased atrial or ventricular diameter, or abnormalities of wall motion, as assessed by echocardiography 1 to 2 hours after the beginning of antihypertensive treatment, when symptoms subsided and BP values were significantly reduced with respect to values on admission.
Ten patients (7 men aged 55.3±4.2 years and 3 women aged 52.2±6.2 years) with mild or moderate essential hypertension (World Health Organization grades I and II; mean duration of hypertension, 32±6 months) were also studied as a hypertensive control group. They were recruited from among individuals attending the Hypertension Clinic at our institution during a period of discontinuation of antihypertensive drugs aimed at therapeutic adjustment. These patients were included in our study only if they did not present any symptoms and their BP was not above 180 mm Hg systolic or 105 mm Hg diastolic 7 days after withdrawal from drugs. BP had been monitored every 30 minutes throughout the 24 hours with a fully automatic recorder set to exclude relevant daily changes. Routine laboratory tests were normal. Four patients presented electrocardiographic or echocardiographic signs of left ventricular hypertrophy; 3 showed echocardiographic signs of mild impairment in cardiac diastolic function; none had ejection fraction less than 55%, increased atrial or ventricular diameter, or abnormalities of wall motion. Patients were placed on a constant sodium (2 to 3 g/d), caffeine-free, and alcohol-free diet for 5 to 6 days before the study.
After BP monitoring for 24 hours, 10 normotensive subjects (6 men aged 54.7±6.0 years and 4 women aged 54.8±3.2 years) without a family history of hypertension served as a normotensive control group. This group was placed on the same diet adopted for the established essential hypertensive group.
Written informed consent was obtained from all participants, and the protocol was approved by the Research Committee of S Orsola Hospital.
Experimental Procedure
The hypertensive patients with an acute increase in BP, hospitalized between 8 AM and noon, were studied immediately after admission and before any antihypertensive treatment. The hypertensive patients with established BP and the normotensive subjects were studied between 8 and 10 AM after an overnight fast; all rested in a supine position for at least 1 hour in a quiet room. During this period, BP and HR were recorded every 15 minutes; only subjects with stable values were included in the study.
All subjects received two infusions via a catheter inserted in the left antecubital vein: the first of saline (0.3 mL/kg IV for 2 minutes), and the second of naloxone hydrochloride (115 µg/kg IV for 2 minutes) 10 minutes later. To achieve a full blockade of all opioid receptor subtypes, we chose this very high dose of naloxone, which we previously found able to trigger maximum inhibition of hormonal and hemodynamic effects of endogenous opioid peptides.18 19
BP, evaluated every 2 minutes, and HR, monitored continuously by electrocardiography, were assessed from the beginning of placebo administration to 20 minutes after naloxone administration in all studied groups.
Blood samples for determination of ß-endorphin, met-enkephalin, dynorphin B, catecholamines, ANF, and ET-1 were taken, through a needle placed in the left forearm vein, 10 minutes after placebo administration and 10 and 20 minutes after naloxone administration. Preliminary observations showed that the peak effect of naloxone in patients with an acute increase in BP occurred 10 minutes after administration (unpublished data, 1994).
BP was determined with a sphygmomanometer cuff placed on the right arm; BP throughout 24 hours was recorded with a fully automatic recorder (Profilomat, Disetronic Medical Systems). Echocardiograms were taken with an MB mode ATL Mark V echocardiograph.
Hormone Assays
Plasma ß-endorphin, met-enkephalin, and dynorphin B levels were radioimmunoassayed after chromatographic preextraction as described previously.19 20 Norepinephrine and epinephrine were determined by column-switching high-performance liquid chromatography with electrochemical detection as detailed previously.21 ANF was determined, after chromatographic preextraction, by a radioimmunoassay procedure according to a previously described method.22
Blood samples (5 mL) for ET-1 determination were placed into cold tubes containing EDTA (1 mL/mg) and aprotinin (500 kallikrein inhibiting units/mL). Blood was centrifuged at 3000 rpm for 15 minutes at 0°C. Plasma was stored at -80°C until assay. Plasma (2 mL) acidified with 0.1% trifluoroacetic acid (TFA, 2 mL) and centrifuged at 3000 rpm for 15 minutes at 0°C was applied to a 200-mg C18 Sep column (Peninsula Laboratories Inc) preactivated with 4 mL of 0.1% TFA and 20 mL of 60% acetonitrile in 0.1% TFA. The column was then washed with 20 mL of 0.1% TFA. ET-1–like material was eluted with 3 mL of 60% acetonitrile in 0.1% TFA. The eluate was dried under nitrogen in a water bath at 40°C and reconstituted in buffer. ET-1 was then measured with a radioimmunoassay kit (Peninsula). The recovery of 125I–ET-1 added to plasma samples was 81±3%. The effective range of the standard curve was between 0.4 and 5.1 fmol/L ET-1 per assay tube; the ED50 was 4.4 fmol/L ET-1 per assay tube. The intra-assay variation was 7.2% and the interassay variation, 11.2%.
Statistical Analysis
We used two-way ANOVA followed by Duncan's test to compare hormonal and hemodynamic values measured 10 minutes after placebo and after naloxone administration in the three groups studied. We used one-way ANOVA to compare the data obtained in hypertensive patients with an acute increase in BP at different time points from naloxone administration. We used Duncan's test for multiple comparisons studied. The degree of association between opioid peptides and catecholamines, opioid peptides and ANF, opioid peptides and ET-1, ANF and catecholamines, ANF and ET-1, and ET-1 and catecholamines as well as between these and hemodynamic parameters was analyzed by Pearson's r correlation coefficient and regression analysis. Values are expressed as mean±SE; a value of P<.05 was considered statistically significant.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
BP and HR After Placebo Administration
BP and HR values were significantly (P<.01) higher in hypertensive patients with an acute increase in BP than in hypertensive and normotensive control groups (Figure). Placebo administration did not change systolic BP, diastolic BP, or HR in any study subjects, independently of their group.
|
), patients with established hypertension (
), and normotensive subjects (
) after placebo (0.3 mL/kg saline IV for 2 minutes) and naloxone hydrochloride (115 µg/kg IV for 2 minutes) administration. *P<.01 vs respective value of patients with established hypertension; 
P<.05, 
P<.01 vs respective value after placebo administration.
BP and HR After Naloxone Administration
In patients with an acute increase in BP, naloxone significantly decreased BP from 2 to 12 minutes after administration and HR from 6 to 12 minutes after administration (Figure). In these patients, HR and BP returned to basal levels at 14 and 18 minutes after naloxone administration, respectively. Naloxone failed to modify BP and HR in the hypertensive and normotensive control groups. BP and HR after naloxone in patients with an acute increase in BP and the hypertensive control group were significantly (P<.01) higher than in the normotensive control group.
Hormonal Parameters After Placebo Administration
Plasma ß-endorphin, met-enkephalin, dynorphin B, norepinephrine, epinephrine, and ANF levels were significantly (P<.01) higher in hypertensive patients with an acute increase in BP than in control groups, whereas plasma ET-1 levels did not differ significantly among the groups (Table). No difference in plasma hormonal concentrations was observed between the patients in whom the BP increase was related to physical as opposed to psychological stress (data not shown). In the hypertensive control group, hormonal values were not significantly different from those of the normotensive control group. In patients with an acute increase in BP and in patients with established hypertension, no significant difference in plasma hormonal levels was observed between those with left ventricular hypertrophy (n=6 and 4, respectively) and those without (n=22 and 6, respectively) or between those with impairment in cardiac diastolic function (n=8 and 3, respectively) and those without (n=20 and 7, respectively) (data not shown).
|
A significant (P<.01) positive correlation was found between ß-endorphin and ANF (r=.64) in patients with an acute increase in BP.
Hormonal Parameters After Naloxone Administration
Ten minutes after administration, naloxone significantly (P<.01) decreased plasma opioid peptide, catecholamine, and ANF values in patients with an acute increase in BP, whereas it did not significantly affect plasma ET-1 concentration (Table). Plasma opioid peptide, catecholamine, and ANF levels significantly (P<.01) differed from those of control groups. Naloxone failed to modify any of the hormonal parameters considered in the hypertensive and normotensive control groups.
In patients with an acute increase in BP, plasma opioid peptide and catecholamine levels 20 minutes after naloxone administration did not differ from those observed 10 minutes after placebo, whereas they significantly (P<.01) differed from those 10 minutes after naloxone. Plasma ANF levels further decreased (P<.01) with respect to levels observed 10 minutes after naloxone administration and did not differ significantly from the values observed in the hypertensive and normotensive control groups. Plasma ET-1 concentration did not change significantly with respect to previous values.
Plasma hormonal concentration assay 20 minutes after naloxone administration was not considered necessary in the control groups because the drug did not significantly change BP or HR.
In patients with an acute increase in BP, a significant positive correlation was found between norepinephrine and systolic BP 10 minutes after naloxone administration (r=.46, P<.01).
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Our findings showed that (1) plasma ß-endorphin, met-enkephalin, dynorphin B, catecholamine, and ANF levels were significantly higher in essential hypertensive patients with a stress-induced acute increase in BP than in patients with established hypertension or in normotensive subjects in resting, stress-free conditions; (2) naloxone-induced inhibition of the endogenous opioid system produced a significant decrease in BP and HR values as well as in plasma opioid peptide, catecholamine, and ANF concentrations in hypertensive patients with an acute increase in BP, whereas it did not affect patients with established hypertension or normotensive subjects; and (3) the effects of naloxone on BP, HR, opioid peptides, and catecholamines were short-lasting, as indicated by the return of these parameters to basal values within 20 minutes after administration.
Our observations are in agreement with the fact that most patients with essential hypertension have the same basal sympathoadrenergic tone as normotensive control subjects.23 24 Nevertheless, they are known to experience episodes of abnormal increases in BP after exposure to psychophysical stressors.15 This phenomenon has been related to an impaired visceral control of cardiovascular functions, resulting in sympathoadrenergic hyperactivity.15 Several works in animals and humans have implicated the opioid peptide system in cardiovascular control,6 12 14 25 but its involvement in coordinating the endocrine and autonomic responses to various forms of stress is still under scrutiny.26 27
The major sources of met-enkephalin and dynorphin are the adrenal medulla and sympathetic nerve endings, where they are coreleased with catecholamines.3 4 ß-Endorphin is primarily secreted from the anterior pituitary together with adrenocorticotropin in response to stress.28 In addition, experimental data suggest that the sympathoadrenergic system participates in the poststress corticotropic activation.29 These findings suggest that the high plasma opioid peptide concentrations observed in patients with an acute increase in BP mainly depend on the hyperactivity of the sympathoadrenergic system.
Interestingly, naloxone administration transiently attenuated the hyperactivity of the sympathoadrenergic system in these patients. Naloxone was consistently effective on all the cardiovascular and endocrine parameters measured, including the opioid peptide levels. The decrease in plasma norepinephrine levels, associated with the fall in systolic BP, suggests that the opioid peptide system, activated by stress-induced sympathoadrenergic hyperactivity, has a role in maintaining an increased sympathetic tone in a sort of positive feedback that naloxone interrupts.
In our patients, the effects of naloxone cannot be purely peripheral. It has been demonstrated that circulating opioid peptides have a direct vasodilator action9 10 and inhibit norepinephrine release from sympathetic nerve terminals.8 30 A putative effect of naloxone on these peripheral targets would have resulted in vasoconstriction, increased norepinephrine release, and elevated BP values. Our results are consistent with the hypothesis that naloxone activity is central and suggest that the opioid system in patients with an acute increase in BP raises the responsiveness of the sympathoadrenergic system by acting on brain regions involved in autonomic and cardiovascular controls.11 31 Anatomic and electrophysiological evidence has shown that various areas related to sympathoadrenergic pathways, such as the paraventricular hypothalamus, the nucleus tractus solitarius, and the ventrolateral medulla, possess opioid receptors6 7 and that opioid peptides are released in the same areas.6 7 Experimental studies have demonstrated that the central opioid system may modulate the development of spontaneous and experimental hypertension in animals.12 Furthermore, animal studies have reported that naloxone inhibits the pressor effect of opioid peptides injected into various brain regions32 and lowers BP levels in stress-induced hypertension by a central mechanism.33
A recent complementary view of central effects of opioid peptides in regulating BP also includes a direct interaction of circulating opioid peptides with central sympathoadrenergic pathways through the blood-brain barrier.34 35 The high circulating levels of opioid peptides measured in our patients could explain the central effects observed after naloxone.
The rapid wearing-off of the hypotensive effects of naloxone was associated with the reappearance of a sympathoadrenergic hyperactivity, as indicated by the increased circulating levels of catecholamines measured 20 minutes after naloxone administration. The short biological half-life of naloxone36 may account for the transient blockade of opioidergic receptors and the reappearance of stimulatory effects of plasma opioid levels on catecholamine release. This may be due to the persistence of opioid peptide system activation and sympathoadrenergic hyperactivity, produced by psychophysical stressors, as indicated by the high circulating levels of opioids and catecholamines after naloxone administration.
In agreement with other studies,13 37 naloxone failed to show any effect on BP in either normotensive or hypertensive subjects included in our study. These findings are consistent with the view that the endogenous opioid system is normally quiescent38 and that it is mainly activated by stressful stimuli that entail important hemodynamic and neuroendocrine adaptations.38
Besides affecting sympathoadrenergic tone, the hyperactivity of the endogenous opioid system in hypertensive patients with an acute increase in BP may also play a role in increasing plasma ANF levels. This is supported by a significant positive correlation between plasma ß-endorphin and ANF levels observed in these patients, but not in patients with established hypertension and in normotensive subjects, and by the powerful effects of naloxone on ANF levels. A study performed in humans during exercise has shown that high plasma ß-endorphin levels stimulate ANF secretion.39 Opiate µ-receptors may be involved in mediating the long-lasting reduction of plasma ANF levels in hypertensive patients with an acute increase in BP after naloxone.40 Naloxone has been reported to have greater potency in antagonizing the effects of µ-agonists than those of other agonists on 
- or 
-opioid receptors.40
Finally, plasma ET-1 concentrations in both groups of hypertensive patients and in normotensive subjects overlapped considerably throughout the study. These findings are in keeping with previous studies that failed to detect elevated peptide levels in patients with hypertension without vascular disease41 42 and/or organ complications, such as congestive heart failure43 and renal insufficiency.44 45 The lack of changes in plasma ET-1 levels after opioid receptor inhibition suggests that the release of this potent vasoconstrictor peptide is not involved in transient changes of BP or sympathoadrenergic tone.
In conclusion, the present results show an activation of the endogenous opioid system associated with a hyperactivity of the sympathoadrenergic system in hypertensive patients with a stress-induced acute increase in BP. The decrease in BP observed after naloxone correlated with the decrease in plasma norepinephrine concentration, suggesting a role for endogenous opioid peptides in maintaining the sympathoadrenergic hyperactivity associated with acute episodes of BP increase in hypertensive patients.
|
Selected Abbreviations and Acronyms |
|---|
|
|
Footnotes |
|---|
Reprint requests to Dr Fiorella Fontana, Istituto di Patologia Speciale Medica e Metodologia Clinica, Ospedale S Orsola, Via Massarenti 9, 40138 Bologna, Italy.
Received July 2, 1996; first decision August 5, 1996; accepted August 5, 1996.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Caffrey JL, Wooldridge CB, Gaugl JF. Naloxone enhances myocardial responses to isoproterenol in dog isolated heart-lung. Am J Physiol. 1986;250:H749-H754.[Medline] [Order article via Infotrieve]
2. Curtis MT, Lefer AM. Protective actions of naloxone in hemorrhagic shock. Am J Physiol. 1980;239:H416-H421.[Medline] [Order article via Infotrieve]
3. Hughes J, Kosterlitz HW, Smith TW. The distribution of methionine-enkephalin and leucine-enkephalin in the brain and peripheral tissues. Br J Pharmacol. 1977;61:639-647.[Medline] [Order article via Infotrieve]
4. Spampinato S, Goldstein A. Immunoreactive dynorphin in rat tissues and plasma. Neuropeptides. 1983;3:193-212.[Medline] [Order article via Infotrieve]
5. Viveros OH, Diliberto EJ, Hazum E, Chang KJ. Opiate-like materials in the adrenal medulla: evidence for storage and secretion with catecholamines. Mol Pharmacol. 1979;16:1101-1108.
6. Stock G, Schmelz M, Knuepfer MM, Forssmann WG. Functional and anatomic aspects of central nervous cardiovascular regulation. In: Ganten D, Pfaff D, eds. Central Cardiovascular Control. New York, NY: Springer-Verlag; 1983:1-24.
7. Yang HYT, Hong JS, Costa E. Regional distribution of leu- and met-enkephalin in rat brain. Neuropharmacology. 1977;16:303-307.[Medline] [Order article via Infotrieve]
8. Gaddis RR, Dixon WR. Modulation of peripheral adrenergic neurotransmission by methionine-enkephalin. J Pharmacol Exp Ther. 1982;221:282-287.
9. Xie CW, Yin LY, Xie XZ, Gao XM, Xia ZA, Chang JK, Tang J. A dynorphin peptide induces hypotension by stimulating the release of atrial natriuretic peptide from rat atrium. Life Sci. 1988;42:1117-1122.[Medline] [Order article via Infotrieve]
10. Catlin DH, Gorelick DA, Gerner RH. Clinical pharmacology of ß-endorphin in depression and schizophrenia. In: Verebey K, ed. Opioids in Mental Illness: Theories, Clinical Observations, and Treatment Possibilities. New York, NY: Annals of the New York Academy of Sciences; 1982:434-447.
11. Chalmers J, Pilowsky P. Brainstem and bulbospinal neurotransmitter systems in the control of blood pressure. J Hypertens. 1991;9:675-694.[Medline] [Order article via Infotrieve]
12. Zamir N, Simantov R, Segal M. Pain sensitivity and opioid activity in genetically and experimentally hypertensive rats. Brain Res. 1980;184:299-310.[Medline] [Order article via Infotrieve]
13. Feuerstein G, Siren AL. The opioid peptides: a role in hypertension? Hypertension. 1987;9:561-565.
14. Guardigli G, Fontana F, Ventura C, Spagnolo N, Bastagli L, Puddu P, Bernardi P. Endogenous opioids and hypertensive crisis in patients with acute cerebrovascular accident. J Endocrinol Invest. 1989;12(suppl 4):9-12.
15. Weiner H. Personality factors and the importance of emotional stresses in hypertension. In: Genest J, Koiw E, Kuchel O, eds. Hypertension: Physiopathology and Treatment. New York, NY: McGraw-Hill Book Co; 1977:661-673.
16. Leino T, Leppaluoto J, Huttunen P, Ruokonen A, Kuronen P. Neuroendocrine responses to real and simulated BA Hawk MK 51 flight. Aviat Space Environ Med. 1995;66:108-113.[Medline] [Order article via Infotrieve]
17. Hirata Y, Itoh KI, Ando K, Endo M, Marumo F. Plasma endothelin levels during surgery. N Engl J Med. 1989;321:1686.[Medline] [Order article via Infotrieve]
18. Fontana F, Bernardi P, Merlo Pich E, Capelli M, Bortoluzzi L, Spampinato S, Canossa M. Relationship between plasma atrial natriuretic factor and opioid peptide levels in healthy subjects and in patients with acute congestive heart failure. Eur Heart J. 1993;14:219-225.
19. Fontana F, Bernardi P, Merlo Pich E, Boschi S, De Iasio R, Capelli M, Carboni L, Spampinato S. Endogenous opioid system and atrial natriuretic factor in normotensive offspring of hypertensive parents at rest and during exercise test. J Hypertens. 1994;12:1285-1290.[Medline] [Order article via Infotrieve]
20. Bernardi P, Fontana F, Merlo Pich E, Spampinato S, Canossa M. Plasma endogenous opioid levels in acute myocardial infarction patients, with and without pain. Eur Heart J. 1992;13:1074-1079.
21. Grossi G, Bargossi AM, Lucarelli C, Paradisi R, Sprovieri C, Sprovieri G. Improvements in automated analysis of catecholamine and related metabolites in biological samples by column switching high-performance liquid chromatography. J Chromatogr. 1991;541:273-284.[Medline] [Order article via Infotrieve]
22. Fontana F, Bernardi P, Spagnolo N, Capelli M. Plasma atrial natriuretic factor in low output heart failure syndromes. Klin Wochenschr. 1990;68:313-319.[Medline] [Order article via Infotrieve]
23. Goldstein DS. Plasma catecholamines and essential hypertension: an analytical review. Hypertension. 1983;5:86-89.
24. Esler M, Jennings G, Biviano B, Lambert G, Hasking G. Mechanism of elevated plasma noradrenaline in the course of essential hypertension. J Cardiovasc Pharmacol. 1986;8(suppl 5):S39-S43.
25. Holaday JW. Cardiovascular effects of endogenous opiate systems. Annu Rev Pharmacol Toxicol. 1983;23:541-594.[Medline] [Order article via Infotrieve]
26. McCubbin JA, Surwit RS, Williams RB Jr. Endogenous opiate peptides, stress reactivity, and risk for hypertension. Hypertension. 1985;7:808-811.
27. McCubbin JA, Surwit RS, Williams RB, Nemeroff CB, McNeilly M. Altered pituitary hormone response to naloxone in hypertension development. Hypertension. 1989;14:636-644.
28. Kjaer A, Knigge U, Bach FW, Warberg J. Stress-induced secretion of pro-opiomelanocortin-derived peptides in rats: relative importance of the anterior and intermediate pituitary lobes. Neuroendocrinology. 1995;61:167-172.[Medline] [Order article via Infotrieve]
29. Gaillet S, Alonso G, Le Borgne R, Barbanel G, Malaval F, Assenmacher I, Szafarczyk A. Effects of discrete lesions in the ventral noradrenergic ascending bundle on the corticotropic stress response depend on the site of the lesion and on the plasma levels of adrenal steroids. Neuroendocrinology. 1993;58:408-419.[Medline] [Order article via Infotrieve]
30. Jarry H, Dietrich A, Barthel A, Giesler A, Wuttke W. In vivo demonstration of a paracrine, inhibitory action of met-enkephalin on adrenomedullary catecholamine release in the rat. Endocrinology. 1989;125:624-629.
31. Quock RM, Kouchich FJ, Vaughn LK, Fries DS. Narcotic antagonist-induced hypotension in the spontaneously hypertensive rat. Life Sci. 1985;37:819-826.[Medline] [Order article via Infotrieve]
32. Schaz K, Stock G, Simon W, Schlor KH, Unger T, Rockhold R, Ganten D. Enkephalin effects on blood pressure, heart rate, and baroreceptor reflex. Hypertension. 1980;2:395-407.
33. Naranjo JR, Urdin MC, Borrel J, Fuentes JA. Evidence for a central but not adrenal opioid mediation in hypertension induced by brief isolation in the rat. Life Sci. 1986;38:1923-1930.[Medline] [Order article via Infotrieve]
34. Schulteis G, Martinez JL Jr. Peripheral modulation of learning and memory: enkephalins as a model system. Psychopharmacology. 1992;109:347-364.[Medline] [Order article via Infotrieve]
35. Martinez JL Jr, Schulteis G, Weinberger SB. How to increase and decrease the strength of memory traces: the effects of drugs and hormones. In: Martinez JL Jr, Kesner RP, eds. Learning and Memory, A Biological View. New York, NY: Academic Press; 1991:149-198.
36. Ngai SH, Berkowitz BA, Yang JC, Hempstead J, Spector S. Pharmacokinetics of naloxone in rats and in man. Anesthesiology. 1976;44:398-401.[Medline] [Order article via Infotrieve]
37. Farsang C, Kapocsi J, Juhasz I, Kunos G. Possible involvement of an endogenous opioid in the antihypertensive effect of clonidine in patients with essential hypertension. Circulation. 1982;66:1268-1272.
38. Gayle AO, Olson RD, Kastin AJ. Endogenous opiates: 1993. Peptides. 1994;15:1513-1556.[Medline] [Order article via Infotrieve]
39. Louisy F, Guezennec CY, Lartigue M, Aldigier JC, Galen FX. Influence of endogenous opioids on atrial natriuretic factor release during exercise in man. Eur J Appl Physiol. 1989;59:34-38.
40. Lord JAH, Waterfield AA, Hughes J, Kosterlitz HW. Endogenous opioid peptides: multiple agonists and receptors. Nature. 1977;267:495-501.[Medline] [Order article via Infotrieve]
41. Naruse M, Kawana M, Hifumi S, Naruse K, Yoshihara I, Oka T, Kato Y, Monzen C, Kurimoto F, Ohsumi K, Hosoda S, Demura H. Plasma immunoreactive endothelin, but not thrombomodulin, is increased in patients with essential hypertension and ischemic heart disease. J Cardiovasc Pharmacol. 1991;17(suppl 7):S471-S474.
42. Nava E, Luscher F. Endothelium-derived vasoactive factors in hypertension: nitric oxide and endothelin. J Hypertens. 1995;13(suppl 2):S39-S48.
43. Pacher R, Bergler-Klein J, Globits S, Teufelsbauer H, Shuller M, Krauter A, Ogris E, Rodler S, Wutte M, Hartter E. Plasma big endothelin-1 concentrations in congestive heart failure patients with or without systemic hypertension. Am J Cardiol. 1993;71:1293-1299.[Medline] [Order article via Infotrieve]
44. Shihiri M, Hirata Y, Ando K, Emori T, Ohta K, Kimoto S, Ogura M, Inoue A, Marumo F. Plasma endothelin levels in hypertension and chronic renal failure. Hypertension. 1990;15:493-496.
45. Tomita K, Ujiie K, Nakanishi T, Tomura S, Matsuda O, Ando K, Shichiri M, Hirata Y, Marumo F. Plasma endothelin levels in patients with acute renal failure. N Engl J Med. 1990;321:1127. Letter.
This article has been cited by other articles:
 |
|
 |
|
  D. Cozzolino, F. C. Sasso, D. Cataldo, D. Gruosso, A. Giammarco, A. Cavalli, C. Di Maggio, G. Renzo, T. Salvatore, D. Giugliano, et al. Acute Pressor and Hormonal Effects of {beta}-Endorphin at High Doses in Healthy and Hypertensive Subjects: Role of Opioid Receptor Agonism J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5167 - 5174. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||