Impairment of the angiotensin-converting enzyme 2–angiotensin-(1-7)-Mas axis contributes to the acceleration of two-kidney, one-clip Goldblatt hypertension

• Published in: Journal of hypertension Vol. 27; no. 10; pp. 1988 - 2000
• Main Authors: Bürgelová, Marcela, Vaňourková, Zdenka, Thumová, Monika, Dvořák, Pavel, Opočenský, Martin, Kramer, Herbert J, Želízko, Michal, Malý, Jan, Bader, Michael, Červenka, Luděk
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins, Inc 01-10-2009; Lippincott Williams & Wilkins
• Subjects: Angiotensin I - blood; Angiotensin I - genetics; Angiotensin I - pharmacology; Angiotensin II - analogs & derivatives; Angiotensin II - blood; Angiotensin II - genetics; Angiotensin II - metabolism; Angiotensin II - pharmacology; Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Blood Pressure - physiology; Cardiology. Vascular system; Cardiomegaly - metabolism; Cardiomegaly - physiopathology; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Disease Models, Animal; Disease Progression; Hypertension, Renovascular - chemically induced; Hypertension, Renovascular - metabolism; Hypertension, Renovascular - physiopathology; Infusion Pumps, Implantable; Medical sciences; Peptide Fragments - blood; Peptide Fragments - genetics; Peptide Fragments - pharmacology; Rats; Rats, Transgenic; Surgical Instruments; Telemetry; Vasodilator Agents - pharmacology; Hypertension; Renal function; Peptide hormone; Cardiovascular disease; two-kidney one-clip Goldblatt hypertension; Clip; Octapeptide; Renin angiotensin system; angiotensin-(1-7); angiotensin-converting enzyme 2; Acceleration; Angiotensin II; renin-angiotensin system
• ISSN: 0263-6352; 1473-5598
• DOI: 10.1097/HJH.0b013e32832f0d06

OBJECTIVERecent studies have shown that the heptapeptide angiotensin-(1-7) [Ang-(1-7)] exerts important vasoactive actions and can act as an endogenous physiological antagonist of angiotensin II (Ang II) within the renin–angiotensin system (RAS). The present study was performed to evaluate the effects, first, of chronic increases of Ang-(1-7) levels, second, of [7-D-Ala], an Ang-(1-7) receptor antagonist, and, third, of an angiotensin-converting enzyme 2 (ACE2) inhibitor on the course of hypertension and of renal function of the nonclipped kidney in two-kidney, one-clip (2K1C) Goldblatt hypertensive rats.
METHODSBlood pressure (BP) was monitored by radiotelemetry. Elevation of the effect of circulating Ang-(1-7) levels was achieved either by chronic subcutaneous infusion of Ang-(1-7) through osmotic minipumps or by employing transgenic rats that express an Ang-(1-7)-producing fusion protein [Ang-(1-7)TGR+/+] (and its control Ang-(1-7)TGR−/−). [7-D-Ala] was also infused subcutaneously and the ACE2 inhibitor was administrated in drinking water. On day 25 after clipping, rats were anesthetized and renal function was evaluated.
RESULTSChronic infusion of Ang-(1-7) did not modify the course of 2K1C hypertension and did not alter renal function as compared with saline vehicle-infused 2K1C rats. Chronic infusion of [7-D-Ala] or treatment with the ACE2 inhibitor worsened the course of hypertension and elicited decreases in renal hemodynamics. [Ang-(1-7)TGR+/+] and [Ang-(1-7)TGR−/−] rats exhibited a similar course of hypertension.
CONCLUSIONThe present data support the notion that Ang-(1-7) serves as an important endogenous vasodilator and natriuretic agent and its deficiency might contribute to the acceleration of 2K1C Goldblatt hypertension.