(Hypertension. 1997;30:535.)
© 1997 American Heart Association, Inc.
Articles |
Counterregulatory Actions of Angiotensin-(1-7)
From the Hypertension Center, the Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC.
Correspondence to Debra I. Diz, PhD, Wake Forest University/Bowman Gray School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1032.
Abstract Angiotensin (Ang)-(1-7) is a bioactive component of the renin-angiotensin system that is formed endogenously from either Ang I or Ang II. The first actions described for Ang-(1-7) indicated that the peptide mimicked some of the effects of Ang II, including the release of prostanoids and vasopressin. However, Ang-(1-7) is devoid of vasoconstrictor, central pressor, or thirst-stimulating actions. In fact, new findings reveal depressor, vasodilator, and antihypertensive actions that may be more apparent in hypertensive animals or humans. Thus, the accumulating evidence suggests that Ang-(1-7) may oppose the actions of Ang II either directly or by stimulation of prostaglandins and nitric oxide. These observations are significant because they may explain the effective antihypertensive action of converting enzyme inhibitors in a variety of non–renin-dependent models of experimental and genetic hypertension as well as most forms of human hypertension. In this context, studies in humans and animals showed that the antihypertensive action of converting enzyme inhibitors correlated with increases in plasma levels of Ang-(1-7). In this review, we summarize our knowledge of the mechanisms accounting for the counterregulatory actions of Ang-(1-7) and elaborate on the emerging concept that Ang-(1-7) functions as an antihypertensive peptide within the cascade of the renin-angiotensin system.
Key Words: angiotensin II • angiotensin receptors • blood pressure • hypertension, essential • rats, inbred SHR
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 R. M. Touyz and E. L. Schiffrin Signal Transduction Mechanisms Mediating the Physiological and Pathophysiological Actions of Angiotensin II in Vascular Smooth Muscle Cells Pharmacol. Rev., December 1, 2000; 52(4): 639 - 672. [Abstract] [Full Text] [PDF]
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A. J. Allred, D. I. Diz, C. M. Ferrario, and M. C. Chappell Pathways for angiotensin-(1---7) metabolism in pulmonary and renal tissues Am J Physiol Renal Physiol, November 1, 2000; 279(5): F841 - F850. [Abstract] [Full Text] [PDF]
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 M. C. DE GRACIA, A. OSUNA, F. O'VALLE, R. G. DEL MORAL, R. WANGENSTEEN, C. G. DEL RIO, and F. VARGAS Deoxycorticosterone Suppresses the Effects of Losartan in Nitric Oxide--Deficient Hypertensive Rats J. Am. Soc. Nephrol., November 1, 2000; 11(11): 1995 - 2000. [Abstract] [Full Text]
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I. Kucharewicz, E. Chabielska, D. Pawlak, T. Matys, R. Rolkowski, and W. Buczko The antithrombotic effect of angiotensin-(1--7) closely resembles that of losartan Journal of Renin-Angiotensin-Aldosterone System, September 1, 2000; 1(3): 268 - 272. [Abstract] [PDF]
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R. K. HANDA Metabolism Alters the Selectivity of Angiotensin-(1-7) Receptor Ligands for Angiotensin Receptors J. Am. Soc. Nephrol., August 1, 2000; 11(8): 1377 - 1386. [Abstract] [Full Text]
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D. Roccatello, G. Mengozzi, G. Gigliola, D. Rossi, R. Mosso, G. Cacace, R. Polloni, G. Cesano, G. Picciotto, L. Paradisi, et al. Effects of angiotensin II blockade on nitric oxide blood levels in IgA nephropathy Nephrol. Dial. Transplant., July 1, 2000; 15(7): 988 - 993. [Abstract] [Full Text] [PDF]
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D. C. Braga, E. Mori, K. T. Higa, M. Morris, and L. C. Michelini Central oxytocin modulates exercise-induced tachycardia Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2000; 278(6): R1474 - R1482. [Abstract] [Full Text] [PDF]
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M. C. Chappell, M. N. Gomez, N. T. Pirro, and C. M. Ferrario Release of Angiotensin-(1-7) From the Rat Hindlimb : Influence of Angiotensin-Converting Enzyme Inhibition Hypertension, January 1, 2000; 35(1): 348 - 352. [Abstract] [Full Text] [PDF]
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 A. Reaux, M. C. Fournie-Zaluski, C. David, S. Zini, B. P. Roques, P. Corvol, and C. Llorens-Cortes Aminopeptidase A inhibitors as potential central antihypertensive agents PNAS, November 9, 1999; 96(23): 13415 - 13420. [Abstract] [Full Text] [PDF]
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R. E. Widdop, D. B. Sampey, and B. Jarrott Cardiovascular Effects of Angiotensin-(1-7) in Conscious Spontaneously Hypertensive Rats Hypertension, October 1, 1999; 34(4): 964 - 968. [Abstract] [Full Text] [PDF]
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K. C Wollert and H. Drexler The renin-angiotensin system and experimental heart failure Cardiovasc Res, September 1, 1999; 43(4): 838 - 849. [Abstract] [Full Text] [PDF]
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A. J. M. Roks, P. P. van Geel, Y. M. Pinto, H. Buikema, R. H. Henning, D. de Zeeuw, and W. H. van Gilst Angiotensin-(1–7) Is a Modulator of the Human Renin-Angiotensin System Hypertension, August 1, 1999; 34(2): 296 - 301. [Abstract] [Full Text] [PDF]
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R. K. Handa Angiotensin-(1-7) can interact with the rat proximal tubule AT4 receptor system Am J Physiol Renal Physiol, July 1, 1999; 277(1): F75 - F83. [Abstract] [Full Text] [PDF]
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A. Kurtz and C. Wagner Role of nitric oxide in the control of renin secretion Am J Physiol Renal Physiol, December 1, 1998; 275(6): F849 - F862. [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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S. N. Iyer, M. C. Chappell, D. B. Averill, D. I. Diz, and C. M. Ferrario Vasodepressor Actions of Angiotensin-(1–7) Unmasked During Combined Treatment With Lisinopril and Losartan Hypertension, February 1, 1998; 31(2): 699 - 705. [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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D. I. Diz, B. Westwood, S. M. Bosch, D. Ganten, and C. Ferrario NK1 Receptor Antagonist Blocks Angiotensin II Responses in Renin Transgenic Rat Medulla Oblongata Hypertension, January 1, 1998; 31(1): 473 - 479. [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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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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