Impairment of the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas axis contributes to the acceleration of two-kidney, one-clip Goldblatt hypertension
Language English Country Netherlands Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Angiotensin I blood genetics pharmacology MeSH
- Angiotensin II analogs & derivatives blood genetics metabolism pharmacology MeSH
- Surgical Instruments MeSH
- Infusion Pumps, Implantable MeSH
- Cardiomegaly metabolism physiopathology MeSH
- Blood Pressure drug effects physiology MeSH
- Rats MeSH
- Disease Models, Animal MeSH
- Peptide Fragments blood genetics pharmacology MeSH
- Rats, Transgenic MeSH
- Disease Progression MeSH
- Hypertension, Renovascular chemically induced metabolism physiopathology MeSH
- Telemetry MeSH
- Vasodilator Agents pharmacology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 7-Ala-angiotensin (1-7) MeSH Browser
- angiotensin I (1-7) MeSH Browser
- Angiotensin I MeSH
- Angiotensin II MeSH
- Peptide Fragments MeSH
- Vasodilator Agents MeSH
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. CONCLUSION: 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.
References provided by Crossref.org
Research on Experimental Hypertension in Prague (1966-2009)
