(Hypertension. 1996;27:523-528.)
© 1996 American Heart Association, Inc.
Articles |
Angiotensin-(1-7) Dilates Canine Coronary Arteries Through Kinins and Nitric Oxide
From the Hypertension Center, the Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC.
Correspondence to K. Bridget Brosnihan, PhD, Hypertension Center, the Bowman Gray School of Medicine of Wake Forest University, Medical Center Blvd, Winston-Salem, NC 27157-1032.
Abstract Angiotensin-(1-7) [Ang-(1-7)] was
recently recognized to have novel biological functions that are
distinct from those of Ang II. In these studies, we determined the
vasoactive effects of Ang-(1-7) together with the
endothelium-dependent mediator(s) of these
responses in canine coronary arteries. Isometric tension was
measured in intact canine coronary artery rings suspended in
organ chambers perfused with 95% O2/5%
CO2 at 37°C. Ang-(1-7) caused significant
concentration-dependent vascular relaxation (2.73±0.58 µmol/L,
EC50) of rings precontracted with the
thromboxane A2 analogue U46,619. Pretreatment
with the nitric oxide synthase inhibitor
N
-nitro-L-arginine (1 mol/L)
abolished the vasodilator response to Ang-(1-7), whereas treatment with
the cyclooxygenase inhibitor
indomethacin (10 µmol/L) was without effect. The
vasodilator response produced by Ang-(1-7) was blocked by 75% with the
bradykinin B2 receptor antagonist Hoe 140 (1
µmol/L) or by 80% with the nonselective Ang II
antagonist [Sar1,Thr8]-Ang
II (1 µmol/L). In contrast, the selective AT1 or
AT2 Ang II antagonists CV 11974 (1 µmol/L)
and PD 123319 (1 µmol/L), respectively, were ineffective in
inhibiting the Ang-(1-7)–elicited vasodilation. Furthermore,
pretreatment of the coronary rings with 2 µmol/L Ang-(1-7)
markedly potentiated the bradykinin response. These results suggest
that Ang-(1-7) elicits coronary vasodilation that is
specifically mediated by the endothelium-dependent
release of nitric oxide. These responses involve a B2
bradykinin receptor and a non-AT1,
non-AT2 angiotensin receptor. These data
suggest that increases in circulating levels of Ang-(1-7) accompanying
long-term administration of converting enzyme
inhibitors or Ang II receptor blockers may contribute to
the cardioprotective actions of these drugs.
Key Words: endothelium-derived relaxing factors • angiotensin peptides • coronary artery • nitric oxide • kinin • prostaglandins
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N. HILL-KAPTURCZAK, M. H. KAPTURCZAK, E. R. BLOCK, J. M. PATEL, T. MALINSKI, K. M. MADSEN, and C. C. TISHER Angiotensin II-Stimulated Nitric Oxide Release from Porcine Pulmonary Endothelium Is Mediated by Angiotensin IV J. Am. Soc. Nephrol., March 1, 1999; 10(3): 481 - 491. [Abstract] [Full Text]
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P. E. Gallagher, P. Li, J. R. Lenhart, M. C. Chappell, and K. B. Brosnihan Estrogen Regulation of Angiotensin-Converting Enzyme mRNA Hypertension, January 1, 1999; 33(1): 323 - 328. [Abstract] [Full Text] [PDF]
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K. Yamada, S. N. Iyer, M. C. Chappell, D. Ganten, and C. M. Ferrario Converting Enzyme Determines Plasma Clearance of Angiotensin-(1–7) Hypertension, September 1, 1998; 32(3): 496 - 502. [Abstract] [Full Text] [PDF]
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G. Gorelik, L. A. Carbini, and A. G. Scicli Angiotensin 1-7 Induces Bradykinin-Mediated Relaxation in Porcine Coronary Artery J. Pharmacol. Exp. Ther., July 1, 1998; 286(1): 403 - 410. [Abstract] [Full Text]
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P. Gohlke, C. Pees, and T. Unger AT2 Receptor Stimulation Increases Aortic Cyclic GMP in SHRSP by a Kinin-Dependent Mechanism Hypertension, January 1, 1998; 31(1): 349 - 355. [Abstract] [Full Text] [PDF]
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S. N. Iyer, C. M. Ferrario, and M. C. Chappell Angiotensin-(1-7) Contributes to the Antihypertensive Effects of Blockade of the Renin-Angiotensin System Hypertension, January 1, 1998; 31(1): 356 - 361. [Abstract] [Full Text] [PDF]
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M. C. Chappell, N. T. Pirro, A. Sykes, and C. M. Ferrario Metabolism of Angiotensin-(1-7) by Angiotensin-Converting Enzyme Hypertension, January 1, 1998; 31(1): 362 - 367. [Abstract] [Full Text] [PDF]
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K. B. Brosnihan, P. Li, D. Ganten, and C. M. Ferrario Estrogen protects transgenic hypertensive rats by shifting the vasoconstrictor-vasodilator balance of RAS Am J Physiol Regulatory Integrative Comp Physiol, December 1, 1997; 273(6): R1908 - R1915. [Abstract] [Full Text] [PDF]
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C. M. Ferrario, M. C. Chappell, E. A. Tallant, K. B. Brosnihan, and D. I. Diz Counterregulatory Actions of Angiotensin-(1-7) Hypertension, September 1, 1997; 30(3): 535 - 541. [Abstract] [Full Text]
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C. V. Lima, R. D. Paula, F. L. Resende, M. C. Khosla, and R. A. S. Santos Potentiation of the Hypotensive Effect of Bradykinin by Short-term Infusion of Angiotensin-(1-7) in Normotensive and Hypertensive Rats Hypertension, September 1, 1997; 30(3): 542 - 548. [Abstract] [Full Text]
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A. Abbas, G. Gorelik, L. A. Carbini, and A. G. Scicli Angiotensin-(1-7) Induces Bradykinin-Mediated Hypotensive Responses in Anesthetized Rats Hypertension, August 1, 1997; 30(2): 217 - 221. [Abstract] [Full Text]
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E. A. Tallant, X. Lu, R. B. Weiss, M. C. Chappell, and C. M. Ferrario Bovine Aortic Endothelial Cells Contain an Angiotensin-(1-7) Receptor Hypertension, January 1, 1997; 29(1): 388 - 392. [Abstract] [Full Text] [PDF]
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P. Li, M. C. Chappell, C. M. Ferrario, and K. B. Brosnihan Angiotensin-(1-7) Augments Bradykinin-Induced Vasodilation by Competing With ACE and Releasing Nitric Oxide Hypertension, January 1, 1997; 29(1): 394 - 398. [Abstract] [Full Text] [PDF]
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E. J. Freeman, G. M. Chisolm, C. M. Ferrario, and E. A. Tallant Angiotensin-(1-7) Inhibits Vascular Smooth Muscle Cell Growth Hypertension, July 1, 1996; 28(1): 104 - 108. [Abstract] [Full Text]
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X.-P. Yang, Y.-H. Liu, D. Mehta, M. A. Cavasin, E. Shesely, J. Xu, F. Liu, and O. A. Carretero Diminished Cardioprotective Response to Inhibition of Angiotensin-Converting Enzyme and Angiotensin II Type 1 Receptor in B2 Kinin Receptor Gene Knockout Mice Circ. Res., May 25, 2001; 88(10): 1072 - 1079. [Abstract] [Full Text] [PDF]
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A. E. Loot, A. J.M. Roks, R. H. Henning, R. A. Tio, A. J.H. Suurmeijer, F. Boomsma, and W. H. van Gilst Angiotensin-(1-7) Attenuates the Development of Heart Failure After Myocardial Infarction in Rats Circulation, April 2, 2002; 105(13): 1548 - 1550. [Abstract] [Full Text] [PDF]
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