(Hypertension. 1996;27:85-89.)
© 1996 American Heart Association, Inc.
Articles |
Kinin-Mediated Antihypertensive Effect of Captopril in Deoxycorticosterone Acetate–Salt Hypertension
From the Department of Pharmacology, University of Minnesota, Minneapolis.
Correspondence to Ben G. Zimmerman, 3-249 Millard Hall, University of Minnesota, 435 Delaware St SE, Minneapolis, MN 55455.
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Abstract |
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Abstract On the basis of evidence suggesting the activation of the kallikrein-kinin system in steroid-induced hypertension, we considered the possibility that the angiotensin-converting enzyme inhibitor captopril would lower the arterial blood pressure in deoxycorticosterone acetate (DOCA)–salt hypertensive rats through kininase II inhibition. In conscious DOCA-salt hypertensive rats with intact kidneys (n=6) or uninephrectomized rats (n=5), the short-term administration of captopril (8 mg/kg IV) decreased mean blood pressure from 141±3 to 118±3 mm Hg (P<.05) and from 176±12 to 158±15 mm Hg (P<.05), respectively. The maximal effect of captopril was manifested between 40 and 50 minutes after its administration, and blood pressure remained depressed for at least 2 hours. The bradykinin B2 receptor antagonist Hoe 140 (500 µg/kg IV) abolished the antihypertensive effect of captopril in the DOCA-salt hypertensive rats, indicating kinin involvement. Losartan, an angiotensin type 1 receptor antagonist, had no effect on blood pressure in another group of DOCA-salt hypertensive rats (n=9) and did not significantly change the response to captopril. No effect of the angiotensin-converting enzyme inhibitor was seen in normotensive control rats (n=5), indicating the absence of a nonspecific hypotensive action of the drug. Plasma renin activity was lower in the DOCA-salt hypertensive rats (0.7±0.2 ng angiotensin I/mL per hour, n=4) than in normotensive control rats (8.8±1.7, n=4). The involvement of kinins in the antihypertensive effect of captopril in DOCA-salt hypertension supports the contention that the kallikrein-kinin system contributes to blood pressure regulation in this hypertension model.
Key Words: desoxycorticosterone • captopril • rats, inbred strains • kallikrein-kinin system
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Introduction |
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Kallikreins are serine proteases that cleave vasodilator peptides, the kinins, from protein precursors known as kininogens that are present in plasma.1 It is thought that the kallikrein-kinin system plays a role in the regulation of systemic BP and renal function,1 2 and this contention has been strengthened by recent evidence for the presence of kallikrein-like enzymes in blood vessels.3 4 These findings have led to the concept of a local kallikrein-kinin system functioning in a paracrine manner2 like that of the local RAS, with the kallikrein-kinin system fulfilling a vasodilator rather than vasoconstrictor role. As with the RAS, there may be little or no tonic activity of the kallikrein-kinin system under normal physiological conditions, but activation is brought about by specific stimuli such as the mineralocorticoids DOCA and aldosterone.5 6 7 It is interesting that kallikrein excretion is augmented in experimental DOCA-salt hypertension and its clinically related form, primary aldosteronism,5 6 whereas it is decreased in essential hypertension in humans and animal models of genetic hypertension.7 8 Thus, when depressed the kallikrein-kinin system may contribute to hypertension, and on activation it may modulate hypertensive processes.
Because the RAS is suppressed in DOCA-salt hypertension, it was assumed that blockers of the system, such as ACE inhibitors or angiotensin antagonists, would not affect BP in this form of hypertension. This seemed to be true, because BP was not reduced during the long-term administration of ACE inhibitors in DOCA-salt hypertension.9 10 11 However, some studies in which ACE inhibitors were administered acutely12 13 or subacutely14 to DOCA-salt hypertensive animals revealed a decrease in BP. Other investigations in the conscious DOCA-salt hypertensive dog15 and anesthetized rat16 failed to detect such an effect. Recent evidence has further supported the concept that kinins play an antihypertensive role in DOCA-salt hypertension.17 18 Because kinins have a potent effect on sodium excretion and RBF, it is conceivable that these renal actions may be responsible for BP modulation in DOCA-salt hypertension.
Some of these results and the knowledge that ACE or kininase II degrades the potent vasoactive peptide bradykinin to inactive fragments suggest the possibility that ACE inhibition could affect BP and renal hemodynamics in DOCA-salt hypertension through a kinin-mediated effect or effects. Because an antihypertensive effect of ACE inhibitors in steroid-induced hypertension and its mechanism have not been firmly established, we conducted the present investigation. We designed experiments (1) to determine whether the short-term administration of captopril to DOCA-salt hypertensive rats lowers BP, (2) to show whether this effect is kinin mediated, and (3) to see whether an angiotensin antagonist alters the effect of the ACE inhibitor. These experiments were conducted in conscious rats instrumented for direct BP recording. In anesthetized DOCA-salt hypertensive rats we examined the effect of captopril on RBF because a renal effect might have contributed to the BP response seen during its short-term administration.
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Methods |
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DOCA-Salt Hypertension
Experiments were conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and with the approval of the local Animal Care Committee. Male Wistar rats (n=40) (Harlan Laboratories, Madison, Wis) weighing 200 to 250 g were fed normal rat chow and allowed free access to water before DOCA administration. For induction of hypertension the rats were given 0.9% saline to drink and twice a week received intramuscular or subcutaneous injections of 10 mg DOCA suspended in sesame oil.
BP Studies in Conscious Rats
Rats in all groups except group
4 had intact kidneys. Group 4
underwent unilateral nephrectomy 2 to 3 days before DOCA and saline
administration. After 3 to 4 weeks of DOCA-salt or vehicle, the rats
weighed 350 to 450 g, and body weight did not differ among the five
groups. Two days before an experiment the rats were
anesthetized with 40 mg/kg IP sodium pentobarbital. The femoral
artery and vein were catheterized with PE-10 tubing connected to larger
bore polyvinyl or Tygon tubing, and the catheters were passed
subcutaneously and exteriorized behind the neck. The catheters were
anchored to the skin and underlying tissue with a suture and
cyanoacrylate and when not in use were filled with heparinized saline
and plugged with a metal stylet. Each rat was placed in a separate cage
and allowed to recover from the surgery for at least 24 hours. On the
day of an experiment systemic arterial BP was recorded
by connecting the arterial catheter to a pressure
transducer (Gould-Statham) while the rat remained in its cage. BP was
recorded continuously on a polygraph (Grass Instruments), and 20 to
30 minutes were allowed for BP to stabilize before an experiment was
started. The BP values presented were obtained by averaging
readings made 1 minute before, 1 minute after, and at the stated time
intervals during an experiment.
Two experiments were conducted on each rat in group 1 (n=6). On the first day a bolus injection of 0.2 mL sterile saline (control for Hoe 140) was injected intravenously 30 minutes before administration of the ACE inhibitor. Captopril was administered at 8 mg/kg, and BP measurements were taken every 10 minutes before and after captopril during the entire 90-minute experimental period. On the second day an experiment was conducted on the same rats for determination of the contribution of kinins to the captopril-induced decrease in BP. Before captopril was given, the bradykinin B2 receptor antagonist Hoe 140 was administered intravenously as a 0.2-mL bolus at 500 µg/kg. An even lower dose, 200 µg, of Hoe 140 was shown to block completely the depressor response to 250 ng bradykinin in the conscious rat.19 BP measurements were made as in the above-described experiments. For determination of whether a reproducible effect of captopril could be obtained on 2 consecutive days as a control for the experiment with the B2 antagonist, the ACE inhibitor was given to six DOCA-salt hypertensive rats in two experiments separated by 24 hours (group 1A).
In Group 1B, 24 hours after femoral artery catheter implantation a 3-mL blood sample was collected from the femoral artery of the DOCA-salt hypertensive (n=4) and normotensive (n=4) rats, and afterwards the rats were killed. PRA was determined by radioimmunoassay with an Ang I–specific antiserum.20
Group 2 (n=5) served as a control for groups 1 and 3 and received a saline vehicle injection instead of DOCA and drank tap water. These rats received captopril 30 minutes after a saline control injection. BP was recorded for the 90-minute experimental period in this as in all groups.
In group 3 (n=9) the Ang II antagonist losartan was injected slowly at 8 mg/kg IV, and after 20 to 30 minutes, 8 mg/kg IV captopril was administered as in group 1. Losartan at 3 mg/kg IV was shown to block the BP response to 0.1 µg/kg IV Ang II by 73% in the conscious rat.21 Thus, we based the doses of Hoe 140 and losartan on those documented in previous studies to block the responses to exogenous bradykinin and Ang II in conscious rats.
Group 4 rats (n=5) underwent two experiments for determination of whether results could be obtained in uninephrectomized DOCA-treated rats that were similar to those in the rats with intact kidneys. The first experiment was carried out as in group 1, and 24 hours later losartan was administered followed by captopril as in group 2. BP determinations were made during the control period, after losartan, and after captopril as described above.
RBF Studies in Anesthetized DOCA-Salt Hypertensive
Rats
DOCA-salt hypertensive rats (n=7) prepared as described
above
for group 1 were used in this part of the study. In general, the
procedure followed was that of Ha and Dunham.22 Rats were
anesthetized with sodium pentobarbital (50 mg/kg IP). Body
temperature was continuously monitored with a digital thermometer and
maintained between 38°C and 38.5°C with incandescent lamps. The
trachea was intubated and kept free of fluid accumulation. For
maintenance of a constant level of anesthesia and
hematocrit, a saline/rat serum (2:1) solution containing sodium
pentobarbital was infused at 120 µL/kg per minute through a PE-50
catheter in the right jugular vein; the dose infused equaled 21 mg/kg
per hour. Another PE-50 catheter was placed in the right carotid artery
and connected to a pressure transducer (Gould-Statham) for monitoring
of BP. The urinary bladder was exposed via a midline incision, and a
polyethylene catheter was inserted to allow the free flow of urine. The
left kidney was exposed through a retroperitoneal flank incision, and
the rat was suspended from a metal stand to facilitate manipulation of
the renal artery. After the artery was exposed, a 33-gauge curved
needle attached to PE-10 tubing was inserted at the origin of the renal
artery and advanced into the artery. A minute drop of cyanoacrylate was
used to secure the needle in place. Heparinized saline infusion was
begun immediately at 100 µL/kg per minute intrarenal
arterial (IA) while the intravenous infusion
was reduced to 80 µL/kg per minute (saline/serum, 1:1). A
precalibrated electromagnetic flow probe of appropriate size (3 to 3.9
mm in circumference) was placed around the artery distal to the needle.
RBF was measured with an electromagnetic flowmeter (Carolina Medical
Electronics). BP and RBF were continuously recorded on a Grass
polygraph. Occlusive zero was obtained by placing a small bulldog clamp
on the renal artery distal to the flow probe, and the procedure was
repeated two to three times over about a 30-minute period until the
zero was reproducible. An interval of at least 30 minutes was allowed
for stabilization of BP and RBF. Hematocrit was checked by sampling
blood from the tail before surgery was begun and again after the
stabilization period. Control measurements were taken and then
captopril was administered in graded doses intrarenal
arterially to localize its effect on the kidney. Each dose
of 1, 2, 4, and 8 µg/kg per minute was infused for 10 minutes. The IA
infusion rate was maintained constant by adjustment of the combination
of drug and heparinized saline totaling 100 µL/kg per minute. At the
end of each experiment acetylcholine bromide was injected in bolus
doses ranging from 200 to 800 ng until a maximal vasodilator response
was elicited. This was done to establish the maximal vasodilator
capacity of the kidney in each rat that received captopril. After the
experimental protocol was completed, occlusion of the renal artery was
repeated to confirm the zero flow level.
Drugs and Chemicals
Captopril was kindly donated by the
Squibb Institute for Medical
Research and Hoe 140 by Hoechst AG. Losartan was kindly
provided by DuPont-Merck Pharmaceutical Co.
Data Analysis
Values are presented as mean±SEM. Data
were subjected
to one-way ANOVA with repeated measures or two-factor nested
ANOVA. Dunnett's and Scheffé's tests were applied to the
means
after the one-way ANOVA. A value of P<.05 was
considered statistically significant.
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Results |
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TopAbstractIntroductionMethods Results Discussion References |
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BP Response to Short-term Captopril Administration in DOCA-Salt Hypertensive (Groups 1 and 1A) and Normotensive (Group 2) Rats: Effect of Kinin Blockade With Hoe 140
At 2 to 3 weeks the mean BP in the DOCA-salt–treated rats (group 1) was significantly higher than in the vehicle-treated normotensive rats (group 2) (141±3 versus 111±3 mm Hg) (Fig 1
). BP was stable in both groups during the 30 minutes
before captopril administration. Captopril caused a gradual decrease in
BP in the DOCA-salt hypertensive rats, achieving statistical
significance at 30 minutes, with the maximal effect at 40 minutes
(118±3 mm Hg), and the BP remained depressed for the remainder of the
experiment. In the normotensive rats, captopril had no effect on
BP.
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The bradykinin B2 receptor antagonist Hoe 140
at 500 µg/kg IV caused a slight decrease in BP, but this effect was
not statistically significant (Fig 2). Hoe 140 was
effective in completely blocking the antihypertensive effect of
captopril in the DOCA-salt hypertensive rats. No decrease in BP was
seen after kinin blockade. In group 1A, there was an identical
response, ie, a decrease in BP, when the dose of captopril was
administered on 2 consecutive days (Fig 3), ruling out
the possibility of tolerance to the ACE inhibitor or a
persistent effect lasting for more than 24 hours. The length of the
latter experiments was extended for an additional 60 minutes after
captopril administration, and it can be seen that the antihypertensive
action lasted for at least 2 hours after dosing. PRA in group 1B
normotensive (n=4) and hypertensive (n=4) rats was
8.8±1.7 and
0.7±0.2 ng Ang I/mL per hour, respectively, and the means differed
statistically (P<.05).
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Effect of Angiotensin Antagonist on BP
Response to Short-term Captopril Administration in DOCA-Salt
Hypertensive Rats (Group 3)
A comparison of the effect of captopril on
the BP of DOCA-salt
rats after administration of either saline or losartan (group
3) is shown in Fig 4. To facilitate statistical
analysis by ANOVA, the number of experiments in the two groups
was equalized by randomly selecting and adding three experiments from
group 1A to the saline-captopril group (n=9). Losartan did
not significantly change BP in the DOCA-salt hypertensive rats, the BP
remaining unaffected during the 30 minutes after administration of the
angiotensin type 1 receptor antagonist (Fig 4).
The subsequent administration of captopril to the
losartan-treated rats decreased BP (P<.05), and
the time of onset and duration of the effect paralleled those
seen in the saline-treated rats. There appeared to be some
attenuation of the BP-lowering response to captopril by
losartan in group 3; however, a comparison of the effect of
captopril in the two groups by two-factor nested ANOVA failed to
reveal a statistically significant treatment factor. When the BP values
obtained at each of the 10-minute intervals after captopril
administration were averaged, the mean decreases were 8±2 and
17±6
mm Hg for losartan plus captopril and captopril alone,
respectively. The difference between these mean values was also not
statistically significant by group t test
(P>.05).
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BP Response to Captopril in Uninephrectomized DOCA-Salt
Hypertensive Rats (Group 4)
The control BP of the uninephrectomized
DOCA-salt hypertensive
rats was higher than in the DOCA-salt hypertensive rats with intact
kidneys (176±12 versus 141±3 mm Hg, P<.05).
Beginning 20
minutes after captopril administration, BP decreased significantly (to
163±13 mm Hg, P<.05), and as in group 1 the maximal
decrease occurred between 40 and 60 minutes (to 158±15 mm Hg,
P<.05). The magnitude of the maximal decrease in BP was
similar to that seen in the rats with intact kidneys. As in group 3,
losartan appeared to slightly attenuate the BP response to
captopril in group 4, but again this effect was not statistically
significant (data not presented).
Effect of Captopril on BP and RBF in Anesthetized
DOCA-Salt–Treated Rats
Control values of BP and RBF and values
after graded doses of IA
infusions of captopril in this group of rats are shown in the
Table. Captopril had no effect on BP except for the
highest dose (8 µg/kg per minute), which decreased BP from 138±6 to
128±7 mm Hg (P<.05). No change in RBF was seen with any
of the four doses of captopril. The kidney of the
DOCA-salt–treated rat had the capability of vasodilating, because
acetylcholine administered IA at the end of these experiments raised
RBF by a mean of 24.3±8.6%. In the normal anesthetized rat
(n=12) (unpublished data, 1995), captopril decreased BP only slightly,
from 128±3.3 to 122.9±3.9 mm Hg, with the highest dose of 8
µg/kg
per minute but increased RBF significantly (P<.05) by
6.8±1.5%, 10.0±1.8%, 15.1±2.0%, and 18.2±2.6% with
the doses of
1, 2, 4, and 8 µg/kg per minute, respectively. The lower doses had no
effect on BP.
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Discussion |
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The main finding in this investigation was the substantial decrease in BP of conscious DOCA-salt hypertensive rats that was evoked by the ACE inhibitor captopril. In DOCA-salt hypertensive rats with intact kidneys (group 1) and also in uninephrectomized rats (group 4) that had an even higher BP, captopril caused a decrease in BP of approximately 20 mm Hg. As seen in group 1A, the effect of captopril on BP lasted for at least 2 hours and thus represented more than a transient response. The BP lowering was not due to some nonspecific effect of the drug because normotensive rats (group 2) were not affected by captopril. Captopril was probably acting by kinin potentiation rather than by blocking the RAS to cause the antihypertensive effect. This statement is based on the following. First, the DOCA-salt regimen resulted in a much attenuated PRA, representing marked suppression of the RAS, and second, losartan had no effect on BP. It is unlikely, therefore, that blockade of the RAS could account for the decrease in BP caused by captopril. Because the BP response to captopril was abolished by Hoe 140, a B2 kinin receptor blocking agent, kinin mediation of the response to captopril is strongly indicated. Administration of the ACE inhibitor ramipril over 1 week caused a gradual lowering of BP in DOCA-salt hypertensive rats, and interestingly this effect was prevented by concomitant dosing with Hoe 140.14 These results of Carretero are quite similar to those of the present study, except that we have demonstrated kinin involvement with the short-term rather than week-long administration of the ACE inhibitor.
Besides blocking the effect of captopril, it might have been expected that the kinin antagonist would have caused a further rise in the BP of the hypertensive rats. Because BP remained unchanged after Hoe 140, it is suggested that in the absence of ACE inhibition the peripheral vasculature of the DOCA-salt hypertensive rats is exposed to a subthreshold vasodilator concentration of kinins. However, when ACE is inhibited, the kinin level is raised above threshold, resulting in vasodilatation and a fall in BP. Madeddu and coworkers18 reported that BP increased to a greater extent in two-kidney DOC-treated (25 mg/wk) rats that were given Hoe 140 over 6 weeks than in rats given DOC alone. The concomitant administration of Hoe 140 and DOC caused a gradual increase in BP that reached a level about 20 mm Hg higher than in the rats given DOC without Hoe 140. The results of the present study, though different in design, appear compatible with the above findings. Our data confirm the presence of a kinin influence in steroid-induced hypertension; however, the short-term administration of Hoe 140 did not reveal that influence in the absence of ACE inhibition. Only after captopril was a kinin-mediated antihypertensive effect uncovered. As suggested by Madeddu et al, sodium retention caused by the antagonism of the natriuretic effect of endogenous kinins by Hoe 140 may be involved in the accentuated hypertension seen in their experiments. Such an action could produce a slowly developing hypertension and explain why an immediate pressor effect of Hoe 140 failed to occur in the present study.
To determine whether captopril had a renal hemodynamic effect in the DOCA-salt hypertensive rat, we infused the drug in graded doses intra-arterially to the kidney. No effect on RBF was observed with any of the four doses; however, BP was decreased by the highest dose of captopril. Apparently, a sufficient quantity of the ACE inhibitor escaped from the kidney to affect the systemic BP. These results suggest that the short-term response to ACE inhibition in the DOCA-salt hypertensive rat is not due to a renal vasodilator effect and that most probably vasodilatation in another regional vascular bed or beds accounts for the BP fall. Our results are in agreement with those of a previous study that reported the lack of effect of intravenously administered enalaprilat on RBF in the anesthetized DOCA-salt hypertensive rat.16 Nakagawa and Nasjletti23 also found no effect on RBF of the combined intravenous administration of captopril and the neutral endopeptidase inhibitor phosphoramidon; however, this drug combination did increase glomerular filtration rate and sodium excretion in anesthetized DOC-treated rats. Because a kinin antagonist reversed these effects, they concluded that kinins were playing a renal regulatory role in DOCA hypertension. Although we did not administer a kinin antagonist in the experiments on anesthetized rats, we did find a difference between the response of the renal vasculature of DOCA-salt–treated and normal rats (unpublished data, 1995) to captopril. RBF in the normal but not the hypertensive rats was increased by ACE inhibition. The difference can be attributed to a normally functioning RAS in the normal rats, whereas it is suppressed in steroid-induced hypertension. It is well known that blockade of the renal influence of an activated RAS results in an increase in RBF. We cannot totally dismiss a renal hemodynamic effect from playing a role in the short-term antihypertensive effect in the conscious DOCA-salt hypertensive rat, because to examine this we used anesthetized rats. There appears to be a difference between the effect of an ACE inhibitor in the conscious and anesthetized DOCA-salt hypertensive rat. In the present study and that of Hollenberg et al,16 BP was decreased only slightly, about 10 mm Hg, in the anesthetized animal. When the rats are conscious BP decreases about 20 mm Hg, suggesting dampening of the response by the anesthetic or surgical trauma. Future experiments should be done in conscious rats to further investigate the mechanism by which ACE inhibitors decrease BP in DOCA-salt hypertension.
To confirm the absence of an RAS influence on the BP of the DOCA-salt hypertensive rat, we tested the effect of the angiotensin type 1 receptor antagonist losartan in the rats in groups 3 and 4. Losartan administered before captopril had no effect on the BP of the DOCA-salt hypertensive rats and insignificantly altered the BP-lowering response to captopril. These results lend further support to our contention that blockade of the RAS did not contribute to the antihypertensive effect of captopril. The absence of effect of an angiotensin antagonist in these experiments and the involvement of kinins in the antihypertensive effect of captopril in this form of hypertension support the view that the kallikrein-kinin system contributes to BP regulation in this hypertension model.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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This research was supported by National Institutes of Health grants HL-44370 and HL-39698.
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Footnotes |
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Previously published in preliminary form (FASEB J. 1995;92:A927).
Received May 22, 1995; first decision July 25, 1995; accepted August 15, 1995.
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References |
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TopAbstractIntroductionMethods Results Discussion References |
|---|
1. Carretero OA, Scicli AG. The renal kallikrein-kinin system. Am J Physiol. 1980;238:F247-F255.
2. Carretero OA, Scicli AG. Local hormonal factors (intracrine, autocrine, and paracrine) in hypertension. Hypertension. 1991;18(suppl I):I-58-I-69.
3. Nolly H, Carretero OA, Lama MC, Miatello R, Scicli AG. Vascular kallikrein in deoxycorticosterone acetate–salt hypertensive rats. Hypertension. 1994;23(suppl I):I-185-I-188.
4.
Madeddu P, Varoni MV, Demontis MP, Fattaccio MC,
Parpaglia PP, Glorioso N. A kallikrein-like enzyme in the
aorta of normotensive and hypertensive rats.
Hypertension. 1994;23:899-902.
5.
Geller GE, Margolius HS, Pisano JJ, Keiser HR.
Effects of mineralocorticoids, altered sodium intake and
adrenalectomy on urinary kallikrein in rats.
Circ Res. 1972;31:857-861.
6.
Margolius HS, Horwitz D, Geller RG, Alexander RW, Gill
JR, Pisano JJ, Keiser HR. Urinary kallikrein excretion in
hypertensive man: relationships to sodium intake and sodium retaining
steroids. Circ Res. 1974;35:820-825.
7. Bhoola KD, Figueroa CD, Worthy K. Bioregulation of kinins: kallikreins, kininogens, and kininases. Pharmacol Rev. 1992;44:1-80. [Medline] [Order article via Infotrieve]
8. Keiser HR, Geller RG, Margolius HS, Pisano JJ. Urinary kallikrein in hypertensive animal models. Fed Proc. 1976;35:199-202. [Medline] [Order article via Infotrieve]
9. Rubin B, Antonaccio MJ, Horovitz ZP. Captopril (SQ 14,225) (D-3-mercapto-3-methylpropanoyl-L-proline): a novel orally active inhibitor of angiotensin converting enzyme and antihypertensive agent. Prog Cardiovasc Dis. 1978;21:184-194.
10. Douglas BH, Langford HG, McCaa RE. Response of mineralocorticoid hypertensive animals to an angiotensin I converting enzyme inhibitor. Proc Soc Exp Biol Med. 1979;161:86-87. [Medline] [Order article via Infotrieve]
11. Wada T, Kanagawa R, Yoshimasa I, Inada Y, Nishikawa K. Role of angiotensin II in cerebrovascular and renal damage in deoxycorticosterone acetate-salt hypertensive rats. J Hypertens. 1995;13:113-122. [Medline] [Order article via Infotrieve]
12. Marks ES, Bing RF, Thurston H, Swales JD. Vasodepressor property of the converting enzyme inhibitor captopril (SQ 14,225): the role of factors other than renin-angiotensin blockade in the rat. Clin Sci. 1980;58:1-6. [Medline] [Order article via Infotrieve]
13. Miyamori I, Brown MJ, Dollery CT. The effect of captopril on blood pressure and plasma renin activity of DOCA-salt hypertensive rats: inhibition of the hypotensive response by indomethacin. Clin Exp Hypertens. 1980;2:935-945.
14. Carretero OA. High-mineralocorticoid conditions: kinins (paracrine hormones) in the regulation of renal function and blood pressure. In: Mornex R, Jaffiol C, Leclere J, eds. Progress in Endocrinology. Proceedings of the Ninth International Congress of Endocrinology, Nice 1992. London, UK: Parthenon; 1993:536-540.
15. Wong PC, Zimmerman BG. Dependence of renal vasodilator effect of captopril on prevailing plasma renin level in the dog: influence of DOCA-salt treatment. Clin Sci. 1982;63:355-360. [Medline] [Order article via Infotrieve]
16. Hollenberg NK, Coletti C, Passan D. Hypertension, volume and vasoconstriction: studies on the renal blood supply in SHR, WKY, and DOCA-salt rat models. Hypertens Res. 1992;15:3-11.
17.
Majima M, Katori M, Hanazuka M, Mizogami S, Nakano T,
Nakao Y, Mikami R, Uryu H, Okamura R, Mohsin SSJ, Oh-Ishi S.
Suppression of rat deoxycorticosterone-salt hypertension by
kallikrein-kinin system. Hypertension. 1991;17:806-813.
18. Madeddu P, Anania V, Parpaglia PP, Demontis MP, Varoni MV, Fattaccio MC, Glorioso N. Chronic kinin receptor blockade induces hypertension in desoxycorticosterone-treated rats. Br J Pharmacol. 1993;108:651-657. [Medline] [Order article via Infotrieve]
19.
Bao G, Gohlke P, Qadri F, Unger T. Chronic kinin
receptor blockade attenuates the antihypertensive effect of
ramipril. Hypertension. 1992;20:74-79.
20. Zimmerman BG, Mommsen C, Kraft E. Renal vasodilatation caused by captopril in conscious normotensive and Goldblatt hypertensive dogs. Proc Soc Exp Biol Med. 1980;164:459-465. [Medline] [Order article via Infotrieve]
21.
Wong PC, Price WA, Chiu AT, Duncia JV, Carini DJ,
Wexler RR, Johnson AL, Timmermans PBMWM. Nonpeptide
angiotensin II receptor antagonists, VIII:
characterization of functional antagonism displayed by DuP 753, an
orally active antihypertensive agent. J
Pharmacol Exp Ther. 1990;252:719-725.
22.
Ha H, Dunham EW. Limited capacity for renal
vasodilatation in anesthetized diabetic rats. Am
J Physiol. 1987;253:H845-H855.
23. Nakagawa M, Nasjletti A. Renal function as affected by inhibitors of kininase II and of neutral endopeptidase 24.11 in rats with and without deoxycorticosterone pretreatment. Agents Action. 1991;247:495-499.
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N.-E. Rhaleb, H. Peng, M. E. Alfie, E. G. Shesely, and O. A. Carretero Effect of ACE Inhibitor on DOCA-Salt– and Aortic Coarctation–Induced Hypertension in Mice : Do Kinin B2 Receptors Play a Role? Hypertension, January 1, 1999; 33(1): 329 - 334. [Abstract] [Full Text] [PDF]
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