(Hypertension. 1995;26:445-451.)
© 1995 American Heart Association, Inc.
Articles |
ß-Adrenergic, Angiotensin II, and Bradykinin Receptors Enhance Neurotransmission in Human Kidney
From Innere Medizin IV und Urologie (W.S.-S.), Universitätsklinik Freiburg (Germany).
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Abstract |
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Abstract The aim of this study was to investigate angiotensin II (Ang II) receptor–, bradykinin receptor–, and ß-adrenergic receptor–mediated modulation of norepinephrine release from human renal sympathetic nerves and to characterize the respective receptor subtypes involved. Human cortical kidney slices were incubated with [3H]norepinephrine, placed in superfusion chambers between two platinum electrodes, and superfused with Krebs-Henseleit solution. The sympathetic nerves were stimulated electrically at 2.5 Hz for 1 minute, and the stimulation-induced outflow of radioactivity was taken as an index of endogenous norepinephrine release. Ang II and its precursor Ang I (both 0.01 to 1 µmol/L) enhanced stimulation-induced outflow of radioactivity in a concentration-dependent manner, with EC50 values of 0.03 and 0.05 µmol/L, respectively. The enhancement by Ang I but not that by Ang II was inhibited by the angiotensin-converting enzyme inhibitor captopril (3 µmol/L). The concentration-response curves of Ang I and Ang II were shifted to the right by EXP 3174 (0.01 µmol), the in vitro active form of the Ang II type 1 receptor antagonist losartan, with affinity estimates of 8.72 and 9.30, respectively. A higher concentration of EXP 3174 (0.1 µmol/L) abolished the facilitatory effects of Ang I and Ang II. The Ang II type 2 receptor antagonist PD 123319 (10 µmol/L) did not alter the facilitation by Ang II. In the absence of other drugs, bradykinin (0.01 to 1 µmol/L) failed to modulate stimulation-induced outflow of radioactivity but in the presence of captopril (3 µmol/L) enhanced it in a concentration-dependent manner, with an EC50 of 0.1 µmol/L. This facilitatory effect of bradykinin was prevented by the bradykinin type 2 receptor antagonist Hoe 140 (0.3 µmol/L). The ß1/ß2-adrenergic receptor agonist isoproterenol (0.001 to 0.1 µmol/L) also enhanced stimulation-induced outflow of radioactivity in a concentration-dependent manner, with an EC50 of 0.008 µmol/L. The facilitatory effect of isoproterenol was abolished by the ß2-adrenergic receptor antagonist ICI 118551 (0.03 µmoL/L) but unaltered by the ß1-adrenergic receptor antagonist atenolol (3 µmol/L), captopril (3 µmol/L), or EXP 3174 (0.1 µmol/L). We conclude that activation of prejunctional Ang II type 1, bradykinin type 2, and ß2-adrenergic receptors facilitates renal norepinephrine release in humans. Ang II can be formed locally within the human renal cortex from Ang I by angiotensin-converting enzyme to activate prejunctional Ang II type 1 receptors. The ß2-adrenergic receptor–mediated effect is likely to function independently of a local renin-angiotensin system. However, the facilitatory bradykinin type 2 receptor mechanism can be demonstrated only when bradykinin degradation is prevented by the angiotensin-converting enzyme (kininase II) inhibitor captopril.
Key Words: kidney • human • norepinephrine • ß-adrenergic receptors • angiotensin II • bradykinin • losartan
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Introduction |
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The sympathetic nervous system regulates many physiological functions of the kidney.1 Thus, firing of the renal sympathetic nerves with an intensity that does not alter renal blood flow leads to enhanced sodium and water retention and stimulates the release of renin from juxtaglomerular cells.2 The amount of the responsible neurotransmitter norepinephrine released from sympathetic nerve terminals can be modulated within the neuroeffector junction through prejunctional receptor systems, which can be activated by endogenous substances or drugs.3 4 5 With respect to the kidney, numerous inhibitory and some facilitatory prejunctional receptor systems have been characterized, almost exclusively in experimental animals.6 7 The classic facilitatory receptor mechanisms are mediated by activation of prejunctional angiotensin II (Ang II) receptors8 9 or prejunctional ß-adrenergic receptors.10 Furthermore, postjunctional ß-adrenergic receptor stimulation by isoproterenol has been shown to induce vascular release of Ang II,11 which may then activate prejunctional Ang II receptors.12 Recently, a technique has been established to study the modulation of norepinephrine release from human renal tissue in vitro13 ; the aim of the present study was therefore to test whether Ang II modulates norepinephrine release in human renal cortex. Furthermore, we set out to characterize the Ang II receptor subtype involved using the nonpeptide Ang II type 1 (AT1) receptor antagonist EXP 3174 and the type 2 (AT2) receptor antagonist PD 123319.14 15 We also investigated the possible interaction of ß-adrenergic receptor–mediated modulation of norepinephrine release with a local renin-angiotensin system. Finally, there are recent indirect reports that in rat atrium16 the endogenous peptide bradykinin has positive inotropic effects caused by facilitation of norepinephrine release by a prejunctional mechanism. This facilitatory effect is more pronounced in the presence of angiotensin-converting enzyme (ACE) inhibition and in accord with previous findings in rat kidney.17 In contrast, in rabbit kidney18 pulmonary artery and heart19 bradykinin seems to inhibit sympathetic neurotransmission. In light of these findings we also tested the effect of bradykinin on norepinephrine release from human renal cortex.
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Methods |
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Patients and Cortical Kidney Slice Preparation
The present in vitro study in human renal cortex was approved by the local ethics committee. Renal cortex tissue was obtained from 28 patients (18 men, 10 women; 31 to 82 years of age; mean, 63.8±2.2 years) undergoing renal surgery because of hypernephroma (23 cases), epithelial carcinoma of the urinary tract (4 cases), or metastasis of a bronchial carcinoma (1 case). Only macroscopically intact renal cortex tissue was used. None of the patients had been treated with drugs known to interact with either the storage or release mechanism of norepinephrine. The renal cortex tissue was transferred into ice-cold Krebs-Henseleit solution immediately after excision and further prepared for experiments not more than 10 minutes later. The renal cortex was cleared of all connective tissue including the capsule, and cortical slices (0.3 mm thick, 6.5 mm in diameter) were prepared.
Experimental Design
The cortical kidney slices were incubated with
(-)-[2,5,6-3H]norepinephrine (42.1
Ci/mmol, 0.5 µmol/L) for 60 minutes in Krebs-Henseleit solution that
was continuously bubbled with carbogen (95% O2 and 5%
CO2). The slices were then placed into six superfusion
chambers (volume of 250 µL) between two platinum electrodes and kept
in a bath at 37°C. The slices were superfused at a constant rate of 2
mL/min with Krebs-Henseleit solution for 101 minutes for removal of
loosely bound radioactivity. After 65 minutes of this washing
procedure, cocaine (10 µmol/L) was added to the superfusion solution,
and a priming stimulation (5 Hz, 1-millisecond pulse width, 20-mA
current strength for 1 minute) was given. After 101 minutes of the
washing, 35 consecutive samples of the superfusate were collected in
3-minute fractions with a fraction collector (Retriever IV, Isco).
There were four stimulation periods (S1 through
S4, each 27 minutes apart, 2.5 Hz, 1-millisecond
pulse width, 20 mA) at 6, 33, 60, and 87 minutes after commencement of
the collections of superfusate. The effect of drugs was tested by
adding them in increasing concentrations to the superfusion solution 12
minutes before S2-S4. In those experiments in
which a drug was present for all stimulation periods (throughout),
the drug was added to the superfusion solution immediately after the
priming stimulation.
Estimation of Radioactivity
The 3-minute samples (6 mL) were mixed with 10 mL scintillation
fluid (Ultima Gold, Packard Canberra GmbH) for measurement of the
amount of radioactivity present in the superfusion solution by
liquid scintillation counting. Total tissue radioactivity was
determined at the end of each experiment. The kidney slices were
dissolved in 1 mL tissue solubilizer (Soluene, Packard Canberra GmbH)
and then mixed with 10 mL scintillation fluid.
Calculation of Results
The spontaneous outflow of radioactivity from the slices was
determined as the mean of the amount of radioactivity in the
superfusate collected during the 3-minute collection period immediately
before and 12 minutes after the onset of stimulation. The
stimulation-induced (S-I) outflow of radioactivity was calculated
by subtracting the spontaneous outflow of radioactivity from the
radioactivity present in the four 3-minute samples collected
immediately after the onset of stimulation. The S-I outflow of
radioactivity was subsequently expressed as a fraction (percentage) of
the total tissue content of radioactivity at the time of stimulation
(fractional S-I outflow of radioactivity [FR]). FR in Sn
(FR2-FR4) was expressed as a percentage of that
in S1 (FRn as percentage of FR1)
and therefore termed S-I outflow ratio. The spontaneous (resting)
outflow of radioactivity during S2-S4 was
expressed as a percentage of that during S1. Since none of
the drugs used had a substantial effect on the resting outflow of
radioactivity compared with control experiments, these data are not
shown. For further evaluation of drug effects on the fractional S-I
outflow of radioactivity, the
FRn/FR1 values were calculated as a
percentage of the values of the corresponding control experiments.
EC50 values (concentrations that inhibited S-I outflow of
radioactivity by 50%) were determined graphically, and the affinity
estimates of antagonist (pKB) were calculated
according to the method of Furchgott20 with the use of the
following equation:
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where EC50' is the EC50 of the agonist in the presence of the antagonist, EC50 is the EC50 of the agonist in the absence of the antagonist, and [A] is antagonist concentration.
All data are expressed as mean±SEM. An agonist effect was tested in each group of experiments (presence or absence of antagonist) against the respective vehicle or antagonist control experiments by Bonferroni-corrected t test. For comparison of the effects of an agonist in the presence of an antagonist with the effects of the same agonist in the absence of any drugs, data were tested for interaction by two-way ANOVA (2x2 experiments). Probability levels of less than .05 were considered statistically significant.
Drugs and Vehicles
The Krebs-Henseleit solution had the following composition
(mmol/L): NaCl 118, KCl 4.7, CaCl2 2.5, MgSO4
0.45, NaHCO3 25, KH2PO4 1.03,
D-(+)-glucose 11.1, disodium edetate 0.067, corticosterone
0.02, and ascorbic acid 0.07.
The following drugs were purchased: levo-[ring-2,5,6-3H]norepinephrine (NEN); corticosterone, (±)-isoproterenol, and Ang I acetate (Sigma Chemical Co); cocaine HCl (E Merck); and bradykinin acetate (Bachem).
The following drugs were generously donated: [Val5]-Ang II (Hypertensin, Ciba-Geigy); captopril HCl (von Heyden); 2-n-butyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole-5-carboxylic acid (EXP 3174, DuPont); erythro-DL-1-(7-methyl-indan-4-yloxy)-3-isopropylaminobutan-2-ol (ICI 118551) and atenolol (ICI); (S)-1-{[4-(dimethylamino)-3-methylphenyl]methyl}-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazol[4,5-c]pyridine-6-carboxylic acid difluoracetate monohydrate (PD 123319, Parke-Davis); and D-Arg,[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin (Hoe 140, Hoechst). All drugs were diluted in distilled water except corticosterone and EXP 3174, which were dissolved in absolute ethanol before being diluted with Krebs-Henseleit solution.
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Results |
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One hundred eighty-four cortical kidney slices (mean wet weight, 15.5±0.3 mg) from 28 patients were incubated with [3H]norepinephrine and superfused with Krebs-Henseleit solution in superfusion chambers between two platinum electrodes. The slices accumulated radioactivity (137700±4600 disintegrations per minute per milligram); the fractional S-I outflow of radioactivity in S1 in the absence and presence of other drugs is shown in the Table. The fractional S-I outflow of radioactivity was reproducible in all four stimulation periods (S1 through S4). In control experiments without drugs present (Fig 1) the FRn/FR1 ratios (FR2/FR1, FR3/FR1, and FR4/FR1) averaged 103.9±2.7%, 100.8±2.6%, and 98.9±2.4% (n=17), respectively. When antagonists were present throughout the entire experiment, the FRn/FR1 ratios were not different from those in the absence of antagonists (data not shown).
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Effects of Ang I and Ang II on Renal
Neurotransmission
Ang I (Fig 2) and Ang II (both 0.01
to 1 µmol/L) (Fig 3) enhanced the
fractional S-I outflow of radioactivity in a
concentration-dependent manner, with EC50 values of
0.05 µmol/L (0.01 to 0.2, n=7) and 0.03 µmol/L (0.01 to 0.1, n=8),
respectively. The concentration-response curve of Ang I (Fig 2) but not that of Ang II (Fig 3) was
shifted to the right by the ACE inhibitor captopril (3
µmol/L). In the presence of the Ang II receptor
antagonist EXP 3174 (0.1 µmol/L) the facilitatory effects
of Ang I (Fig 2) and Ang II (Fig 3) were
abolished. A 10- fold lower concentration of EXP 3174 (0.01 µmol/L)
shifted the concentration-response curves of Ang I (Fig 2) and Ang II (Fig 3) potently to the
right without suppression of the maximum. The EC50 values
for Ang I (0.1 to 10 µmol/L) and Ang II (0.1 to 3 µmol/L) were then
0.5 µmol/L (0.5 to 0.6, n=4) and 0.7 µmol/L (0.4 to 0.8, n=4),
respectively. The calculated affinity estimates for EXP 3174 against
Ang I and Ang II were 8.72 (7.98 to 9.22, n=6) and 9.30 (9.15 to 9.43,
n=8), respectively. In contrast, the AT2 receptor
antagonist PD 123319 (10 µmol/L) did not have any
significant effect on the facilitation induced by Ang II (Fig 3). Neither captopril (0.03 to 3 µmol/L) nor EXP 3174
(0.01 to 1 µmol/L) significantly altered the fractional S-I outflow
of radioactivity (data not shown).
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) and in the presence of 3 µmol/L captopril (A, 
), 0.1
µmol/L EXP 3174 (A, 
), and 0.01 µmol/L EXP 3174 (B,
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), 0.1
µmol/L EXP 3174 (A, 
), 0.01 µmol/L EXP 3174 (B, 
). All data are mean±SEM of three to
eight experiments. *Significant effect of angiotensin II
compared with vehicle control experiments (P<.05 by
modified t test according to Bonferroni); +significant
effect of treatment by EXP 3174 (P<.05 by ANOVA).
Effect of Isoproterenol on Renal Neurotransmission
The ß1/ß2-adrenergic receptor
agonist isoproterenol (0.001 to 0.1 µmol/L) enhanced the fractional
S-I outflow of radioactivity (Fig 4) in a
concentration-dependent manner, with an EC50 of 0.008
µmol/L (0.002 to 0.02, n=10). The facilitatory effect of
isoproterenol was abolished by the ß2-adrenergic receptor
antagonist ICI 118551 (0.03 µmol/L) (Fig 4). The ß1-adrenergic receptor
antagonist atenolol (3 µmol/L), captopril (3 µmol/L),
and EXP 3174 (0.1 µmol/L) did not shift the
concentration-response curve of isoproterenol significantly to the
right (Fig 4).
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Effect of Bradykinin on Renal Neurotransmission
In the absence of other drugs, bradykinin (0.01 to 1 µmol/L) did
not significantly alter fractional S-I outflow of radioactivity (Fig 5). When captopril (3 µmol/L) was
present throughout the entire experiment, bradykinin enhanced S-I
outflow of radioactivity in a concentration-dependent manner, with
an EC50 of 0.1 µmol/L (0.01 to 0.3, n=6). The
facilitatory effect of bradykinin in the presence of captopril (3
µmol/L) was blocked by the bradykinin B2 receptor
antagonist Hoe 140 (0.3 µmol/L) (Fig 5).
Hoe 140 (0.03 to 3 µmol/L) did not significantly alter the fractional
S-I outflow of radioactivity (data not shown).
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Discussion |
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Electrical stimulation of human cortical kidney slices preincubated with [3H]norepinephrine at 2.5 Hz induces the release of radioactivity, which reflects exocytotic, neuronal norepinephrine release.13 21 Thus, in the present study the fractional S-I outflow of radioactivity was taken as an index of endogenous norepinephrine release. A stimulation frequency of 2.5 Hz is in the physiological range of renal sympathetic nerve activity; however, with respect to functional relevance, one has to bear in mind that the pattern of electrical stimulation used in the present study is not identical to that of physiological renal nerve firing.
Ang I and Ang II
The Ang II precursor Ang I enhanced S-I outflow of radioactivity
in a concentration-dependent manner, and this effect was markedly
inhibited by the ACE inhibitor captopril. Ang II also
enhanced S-I outflow of radioactivity in a concentration-dependent
manner, and this effect was unaltered by captopril. This suggests that
in the superfused human renal cortex Ang I is converted to Ang II to
facilitate norepinephrine release. Similar data have been
obtained previously in rat perfused kidney,17 22 rat
superfused renal cortex,23 and dog kidney in
vivo.24 The facilitatory effect of Ang II on
neurotransmission was obtained in the presence of cocaine and was
therefore independent of neuronal uptake blockade by Ang
II,8 24 which is in accord with recent observations in the
perfused rat hind limb.25 It is noteworthy that even in
the presence of a high concentration of captopril (3 µmol/L), Ang I
(1 µmol/L) still slightly but significantly enhances the S-I outflow
of radioactivity from the human renal cortex. This may suggest that at
least under in vitro conditions other enzyme systems besides ACE may be
able to convert Ang I to Ang II. Other Ang II–generating enzymes
may include tissue plasminogen activator,
cathepsin G, tonin, and elastase.26 Ang II has been
shown to mediate its physiological effects via
either AT1 or AT2 receptors, and both subtypes
have been cloned.27 In human kidney AT1 and
AT2 receptors seem to be present, but most of the renal
effects of Ang II seem to be mediated via AT1
receptors.15 28 In human fetal kidney, however, binding
studies have revealed that AT2 receptors predominate;
moreover, in neuronal cultures of neonatal rat brains and PC12W cells,
activation of AT2 receptors by Ang II has been shown to
decrease cGMP levels.28 However, in the present study
the AT2 receptor antagonist PD
12331914 15 failed to influence the facilitatory effect of
Ang II on norepinephrine release even at a concentration of
10 µmol/L. In contrast, the AT1 receptor
antagonist EXP 3174 potently inhibited the facilitatory
effect of Ang I and Ang II, with high-affinity estimates of 8.72
and 9.30, respectively. This suggests that activation of prejunctional
AT1 receptors located on sympathetic nerve endings in human
renal cortex facilitates norepinephrine release. Similar
conclusions have been drawn previously for dog kidney in
vivo.29 In the present study neither EXP 3174 nor
captopril by themselves significantly altered S-I outflow of
radioactivity, suggesting that under the experimental conditions used,
endogenous Ang II does not activate prejunctional
Ang II receptors to enhance norepinephrine release in human
kidney cortex. Although prejunctional Ang II effects are firmly
established for animals in vitro and in vivo,3 4 5 6 7 8 9 14 there
are only a few reports in humans. Recently, it has been shown that Ang
II facilitates norepinephrine release in human isolated
atria via a losartan-sensitive receptor
pathway30 ; however, in vivo the evidence for a
prejunctional facilitatory effect of Ang II is
controversial31 32 and seems to depend on the state of
sympathetic nervous activity.32
ß-Adrenergic Receptors and ACE Inhibition
Facilitation of norepinephrine release by
activation of prejunctional ß2-adrenergic receptors has
been shown in many species and tissues,3 4 5 10 including
rat kidney.22 33 Moreover, these receptors may be
activated by endogenous
epinephrine34 35 to induce certain forms of
hypertension in humans.36 Such prejunctional
ß2-adrenergic receptors also seem to be present in
human renal cortex, because the facilitatory effect of the nonselective
ß-adrenergic receptor agonist isoproterenol on
norepinephrine release was blocked by the
ß2-adrenergic receptor–selective
antagonist ICI 11855137 but not by the
ß1-adrenergic receptor–selective
antagonist atenolol. The concept of prejunctional
ß2-adrenergic receptors was recently challenged by the
finding that activation of postjunctional ß-adrenergic receptor
induces vascular release of Ang II,11 which then may act
transjunctionally to activate prejunctional facilitatory Ang II
receptors.12 38 However, this view was not supported by
subsequent studies in isolated tissues of rats23 39 40 and
guinea pigs.41 Furthermore, in human atrium prejunctional
ß-adrenergic receptors but not Ang II receptors have been shown
to be linked to an adenylate cyclase
pathway.30 Accordingly, in the human superfused renal
cortex the facilitatory effect of isoproterenol was entirely unaltered
by EXP 3174 at a concentration of 0.1 µmol/L, which had abolished the
facilitatory effect of exogenous Ang II (0.01 to 1 µmol/L). Thus,
ß-adrenergic receptor–mediated enhancement does not depend
on the activation of AT1 receptors. The ACE
inhibitor captopril shifted the concentration-response
curve of isoproterenol slightly but not significantly to the right. If
this slight shift was due to prevention of isoproterenol-induced
Ang II formation, then captopril by itself should have inhibited S-I
outflow of radioactivity caused by prevention of Ang II formation by
neuronally released norepinephrine. However, this was not
the case, and therefore the small inhibitory effect of
captopril on ß2-adrenergic receptor–mediated
facilitation remains unclear.
Bradykinin and ACE Inhibition
Bradykinin is a locally occurring peptide. There are several
controversial reports in the literature with respect to modulation of
norepinephrine release.42 Stimulatory effects
of bradykinin on sympathetic neurotransmission have been found in rat
kidney17 and vas deferens,43 pithed
rat,44 and canine blood-perfused gracilis muscle in
situ45 ; whereas in rabbit18 and
canine46 kidney, rabbit pulmonary artery and
heart17 bradykinin seems to inhibit
norepinephrine release. The lack of an effect by bradykinin
in some tissues may partly depend on its fast breakdown by kininase II,
which is identical to ACE.47 In line with this assumption,
bradykinin up to 1 µmol/L failed to alter sympathetic
neurotransmission in the present study in human renal cortex in the
absence of ACE inhibition. However, in the presence of captopril
bradykinin significantly stimulated norepinephrine outflow,
and this effect was blocked by the bradykinin B2 receptor
antagonist Hoe 140. The physiological
concentration of bradykinin occurring at the neuroeffector junction is
not known; however, it must be acknowledged that even in the presence
of captopril, rather large doses of exogenous bradykinin are necessary
to facilitate norepinephrine release in human renal
cortex.
Conclusion
The present study demonstrates three distinct facilitatory
prejunctional mechanisms in human renal cortex.
ß2-Adrenergic receptor and Ang II receptor modulation of
renal norepinephrine release function independently;
however, the ACE activity seems to play a significant role in limiting
prejunctional effects of bradykinin in human kidney. These human renal
cortex receptor systems may be future targets of drug therapy in
primary and secondary renal hypertension.
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Acknowledgments |
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This study was supported by the Deutsche Forschungsgemeinschaft (Ru 401/1-3).
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Footnotes |
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Reprint requests to Dr L.C. Rump, Medizinische Universitätsklinik Freiburg, Innere Medizin IV, Hugstetter Str 55, D-79106 Freiburg, FRG.
Received February 13, 1995; first decision March 17, 1995; accepted June 16, 1995.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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1. DiBona GF. The functions of the renal nerves. Rev Physiol Biochem Pharmacol. 1982;94:75-181.
2. DiBona GF. Neural control of renal function. Fed Proc. 1985;44:2815-2850.
3. Starke K. Regulation of noradrenaline release by presynaptic receptor systems. Rev Physiol Biochem Pharmacol. 1977;77:1-124. [Medline] [Order article via Infotrieve]
4. Westfall TC. Local regulation of adrenergic transmission. Physiol Rev. 1977;7:659-728.
5. Rand MJ, Majewski H, Story DF. Modulation of neuroeffector transmission. In: Antonaccio M, ed. Cardiovascular Pharmacology. New York, NY: Raven Press Publishers; 1990:229-292.
6. Rump LC. Modulation of renal noradrenaline release by prejunctional receptor systems in vitro. Clin Exp Pharmacol Physiol. 1987;14:423-427. [Medline] [Order article via Infotrieve]
7. Rump LC, Schollmeyer P. Modulation der renalen Transmitter-Freisetzung durch präsynaptische Rezeptoren. Klin Wochenschr. 1989;67:865-869. [Medline] [Order article via Infotrieve]
8. Starke K. Beziehungen zwischen dem Renin-Angiotensin-System und dem vegetativen Nervensystem. Klin Wochenschr. 1972;50:1069-1081. [Medline] [Order article via Infotrieve]
9.
Reid IA. Interactions between Ang II,
sympathetic nervous system, and baroreceptor reflexes in regulation of
blood pressure. Am J Physiol. 1992;262:E763-E778.
10. Majewski H. Modulation of noradrenaline release through activation of presynaptic ß-adrenoceptors. J Auton Pharmacol. 1983;3:47-60. [Medline] [Order article via Infotrieve]
11. Nakamura M, Jackson EK, Inagami T. Beta-adrenoceptor-mediated release of angiotensin II from mesenteric arteries. Am J Physiol. 1986;250:H144-H148.
12. Schlicker E, Erkens K, Göthert M. Probable involvement of vascular angiotensin II formation in the ß2-adrenoceptor mediated facilitation of the neurogenic vasopressor response in the pithed rat. Naunyn Schmiedebergs Arch Pharmacol. 1988;338:536-542. [Medline] [Order article via Infotrieve]
13. Rump LC, Schwertfeger E, Schuster MJ, Schaible U, Frankenschmidt A, Schollmeyer PJ. Dopamine DA2-receptor activation inhibits noradrenaline release in human kidney slices. Kidney Int. 1993;43:197-204. [Medline] [Order article via Infotrieve]
14. Timmermans PBMWM, Wong PC, Chiu AT, Herblin WF, Benfield P, Carini DJ, Lee RJ, Wexler RR, Saye JAM, Smith RD. Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol Rev. 1993;45:205-251. [Medline] [Order article via Infotrieve]
15. De Gasparo M, Levens NR. Pharmacology of angiotensin II receptors in the kidney. Kidney Int. 1994;46:1486-1491. [Medline] [Order article via Infotrieve]
16.
Minshall RD, Yelamanchi VP, Djokovic A, Miletich DJ,
Erdös EG, Rabito SF, Vogel SM. Importance of sympathetic
innervation in the positive inotropic effects of bradykinin and
ramiprilat. Circ Res. 1994;74:441-447.
17.
Böke T, Malik KU. Enhancement by locally
generated angiotensin II of release of the adrenergic
transmitter in the isolated rat kidney. J
Pharmacol Exp Ther. 1983;226:900-907.
18. Malik KU, Nasjletti A. Attenuation by bradykinin of adrenergically-induced vasoconstriction in the isolated perfused kidney of the rabbit: relationship to prostaglandin synthesis. Br J Pharmacol. 1979;67:269-275. [Medline] [Order article via Infotrieve]
19. Starke K, Peskar BA, Schumacher KA, Taube HD. Bradykinin and postganglionic sympathetic transmission. Naunyn Schmiedebergs Arch Pharmacol. 1977;299:23-32. [Medline] [Order article via Infotrieve]
20. Furchgott RF. The classification of adrenoceptors (adrenergic receptors): an evaluation from the standpoint of receptor theory. In: Blaschko H, Muscholl E, eds. Catecholamines: Handbook of Experimental Pharmacology. Berlin, FRG: Springer; 1972;33:283-335.
21.
Trendelenburg AU, Limberger N, Rump LC.
2-Adrenergic receptors of the 2C subtype
mediate inhibition of norepinephrine release in human
kidney cortex. Mol Pharmacol. 1994;45:1168-1176. [Abstract]
22.
Rump LC, Majewski H. Beta-adrenoceptor
facilitation of norepinephrine release is not dependent on
local angiotensin II formation in the rat isolated
kidney. J Pharmacol Exp Ther. 1987;243:1107-1112.
23. Rump LC, Schuster MJ, Wilde K, Schollmeyer P. Modulation of noradrenaline release from rat cortical kidney slices: effects of angiotensin I and II. Br J Clin Pharmacol. 1990;30:168s-170s.
24.
Zimmerman BG, Gisslen J. Pattern of renal
vasoconstriction and transmitter release during sympathetic stimulation
in the presence of angiotensin and cocaine.
J Pharmacol Exp Ther. 1968;163:320-329.
25.
Hilgers KF, Veelken R, Rupprecht G, Reeh PW, Luft FC,
Mann JFE. Angiotensin II facilitates sympathetic
transmission in rat hind limb circulation.
Hypertension. 1993;21:322-328.
26. Dzau VJ, Sasamura H, Hein L. Heterogeneity of angiotensin synthetic pathways and receptor subtypes: physiological and pharmacological implications. J Hypertens. 1993;11(suppl 3):S13-S18.
27. Dzau VJ, Mukoyama M, Pratt RE. Molecular biology of angiotensin receptors: target for drug research? J Hypertens. 1994;12(suppl 2):S1-S5.
28. Edwards RM, Aiyar N. Angiotensin II receptor subtypes in the kidney. J Am Soc Nephrol. 1993;3:1643-1652. [Abstract]
29.
Wong PC, Hart SD, Timmermans PBMWM. Effect of
angiotensin II antagonism on canine renal sympathetic nerve
function. Hypertension. 1991;17:1127-1134.
30.
Rump LC, Schwertfeger E, Schaible U, Fraedrich G,
Schollmeyer P. ß2-Adrenergic receptor and
angiotensin II receptor modulation of sympathetic
neurotransmission in human atria. Circ
Res. 1994;74:434-440.
31. Mendelsohn FAO, Doyle SE, Gray GW. Lack of response of sympathetic nervous system to angiotensin infusion. Lancet. 1980;1:492-493.
32. Webb DJ, Seidelin PH, Benjamin N, Collier JG, Struthers AD. Sympathetically mediated vasoconstriction is augmented by angiotensin in man. J Hypertens. 1988;6(suppl 4):S542-S543.
33.
Ekas RD, Steenberg ML, Woods MS, Lokhandwala MF.
Presynaptic - and ß-adrenoceptor stimulation and
norepinephrine release in the spontaneously hypertensive
rat. Hypertension. 1983;5:198-204.
34. Majewski H, Rand MJ. A possible role of epinephrine in the development of hypertension. Med Res Rev. 1986;6:467-486. [Medline] [Order article via Infotrieve]
35. Borkowski KR. Pre- and postjunctional ß-adrenoceptors and hypertension. J Auton Pharmacol. 1988;8:153-171. [Medline] [Order article via Infotrieve]
36.
Floras JS. Epinephrine and the
genesis of hypertension. Hypertension. 1992;19:1-18.
37. Bilski AJ, Halliday SE, Fitzgerald JD, Wale JL. The pharmacology of a ß2-selective adrenoceptor antagonist (ICI 118551). J Cardiovasc Pharmacol. 1983;5:430-437. [Medline] [Order article via Infotrieve]
38. Göthert M, Kollecker P. Subendothelial ß2-adrenoceptors in the rat vena cava: facilitation of noradrenaline release via angiotensin II synthesis. Naunyn Schmiedebergs Arch Pharmacol. 1986;334:156-165. [Medline] [Order article via Infotrieve]
39. Li C, Majewski H, Rand MJ. Facilitation of noradrenaline release from sympathetic nerves in rat anococcygeus muscle by activation of prejunctional ß2-adrenoceptors and angiotensin II receptors. Br J Pharmacol. 1988;95:385-392. [Medline] [Order article via Infotrieve]
40. Rajanayagam AS, Musgrave IF, Rand MJ, Majewski H. Facilitation of noradrenaline release by isoprenaline is not mediated by angiotensin II in mouse atria and rat tail artery. Arch Int Pharmacodyn Ther. 1989;299:185-199. [Medline] [Order article via Infotrieve]
41. Kuwahara M, Kubo T, Misu Y. Isoproterenol-induced facilitation of noradrenaline release does not primarily involve a local angiotensin II mechanism in guinea pig pulmonary arteries. Jpn J Pharmacol. 1989;51:302-305. [Medline] [Order article via Infotrieve]
42. Schwieler JH, Hjemdahl P. Influence of angiotensin-converting enzyme inhibition on sympathetic neurotransmission: possible role of bradykinin and prostaglandins. J Cardiovasc Pharmacol. 1992;20(suppl 9):S39-S46.
43. Llona I, Galleguillos X, Belmar J, Huidobro-Toro JP. Bradykinin modulates the release of noradrenaline from vas deferens nerve terminals. Life Sci. 1991;48:2585-2592. [Medline] [Order article via Infotrieve]
44. Dominiak P, Simon M, Blöchl A, Brenner P. Changes in peripheral sympathetic outflow of pithed spontaneously hypertensive rats after bradykinin and DesArg-bradykinin infusions: influence of converting-enzyme inhibition. J Cardiovasc Pharmacol. 1992;20(suppl 9):S35-S38.
45. Schwieler JH, Kahan T, Nussberger J, Hjemdahl P. Influence of the renin-angiotensin system on sympathetic neurotransmission in canine skeletal muscle in vivo. Naunyn Schmiedebergs Arch Pharmacol. 1991;343:166-172. [Medline] [Order article via Infotrieve]
46. Susic H, Nasjletti A, Malik KU. Bradykinin effects on adrenergic transmission in the canine kidney: relation to prostaglandins. Am J Physiol. 1981;241:R146-R151.
47. Skidgel RA. Bradykinin-degrading enzymes: structure, function, distribution, and potential roles in cardiovascular pharmacology. J Cardiovasc Pharmacol. 1992;20(suppl 9):S4-S9.
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