title: Impairment of the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas axis contributes to the acceleration of two-kidney, one-clip Goldblatt hypertension.
abstract: OBJECTIVE
  Recent 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.
  
  
  METHODS
  Blood 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.
  
  
  RESULTS
  Chronic 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.
  
  
  CONCLUSIONS
  The 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.
authors: Department of Nephrology, Transplant Center, Czech Republic.
authors: Marcela
authors: M
authors: Bürgelová
authors: Zdenka
authors: Z
authors: Vanourková
authors: Monika
authors: M
authors: Thumová
authors: Pavel
authors: P
authors: Dvorák
authors: Martin
authors: M
authors: Opocenský
authors: Herbert J
authors: HJ
authors: Kramer
authors: Michal
authors: M
authors: Zelízko
authors: Jan
authors: J
authors: Malý
authors: Michael
authors: M
authors: Bader
authors: Ludek
authors: L
authors: Cervenka
mesh_terms: D000803:Angiotensin I / Q000097:blood / Q000235:genetics* / Q000494:pharmacology*; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D006332:Cardiomegaly / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D006978:Hypertension, Renovascular / Q000139:chemically induced* / Q000378:metabolism* / Q000503:physiopathology; D015918:Infusion Pumps, Implantable; D010446:Peptide Fragments / Q000097:blood / Q000235:genetics* / Q000494:pharmacology*; D051381:Rats; D055647:Rats, Transgenic; D013525:Surgical Instruments; D013686:Telemetry; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: C092006:7-Ala-angiotensin (1-7); D010446:Peptide Fragments; D014665:Vasodilator Agents; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7)