ave-0991 and Hypotension
ave-0991 has been researched along with Hypotension* in 2 studies
Other Studies
2 other study(ies) available for ave-0991 and Hypotension
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Evidence for Mas-mediated bradykinin potentiation by the angiotensin-(1-7) nonpeptide mimic AVE 0991 in normotensive rats.
We evaluated the effect of the nonpeptide mimic of angiotensin (Ang)-(1-7), AVE 0991, on the hypotensive effect of bradykinin (BK). Increasing doses of intra-arterial or intravenous BK were administered before and 30 minutes after the beginning of AVE 0991 infusion. The effect of AVE 0991 on plasma Ang-converting enzyme activity was tested using Hip-His-Leu as the substrate. The interaction of AVE 0991 with Ang-converting enzyme in vivo was tested by determining its effect on the pressor action of Ang I or Ang II. AVE 0991 produced a significant and similar potentiation of intra-arterial or intravenous bradykinin. AVE 0991 did not inhibit plasma Ang-converting enzyme activity in vitro or the pressor effect of Ang I in vivo. N(W)-nitro-l-arginine methyl ester or D-Ala(7)-Ang-(1-7) administration abolished the BK potentiating effect of AVE 0991. We further examined the BK-potentiating effect of AVE 0991, evaluating its effect on NO production in rabbit endothelial cells. The NO release was measured using the 4-amino-5-methylamino-2'-7'-difluorofluorescein diacetate. A synergistic effect of AVE 0991 and BK on NO release was observed. These results suggest that AVE 0991 potentiates bradykinin through an Ang-converting enzyme-independent, NO-dependent receptor Mas-mediated mechanism. This effect may contribute to the improvement of endothelial function by AVE 0991 in vivo. Topics: Angiotensin I; Angiotensin II; Animals; Bradykinin; Dose-Response Relationship, Drug; Drug Synergism; Endothelium, Vascular; Enzyme Inhibitors; Hypotension; Imidazoles; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Peptide Fragments; Peptidyl-Dipeptidase A; Proto-Oncogene Mas; Proto-Oncogene Proteins; Rabbits; Rats; Rats, Wistar; Receptors, G-Protein-Coupled; Vasodilator Agents | 2007 |
Short-term angiotensin(1-7) receptor MAS stimulation improves endothelial function in normotensive rats.
In this study we evaluated the effect of angiotensin(1-7) and its nonpeptide analog, AVE 0991, on the endothelial function in vivo. The experiments were performed in conscious adult male Wistar rats, with polyethylene catheters implanted into the descending aorta (through left carotid artery), for injection of acetylcholine or sodium nitroprusside, femoral artery for mean arterial pressure and heart rate measurement; and femoral vein for drug administration. Increasing doses of acetylcholine (3.1 ng to 25.0 ng) or nitroprusside (1.0 microg to 10.0 microg) were administered before and 30 minutes after the start of the infusion of: angiotensin(1-7) (0.7 and 7.0 pmol/min); A-779 (180 pmol/min); angiotensin(1-7) (7.0 pmol/min) combined with A-779 (180 pmol/min); AVE 0991 (11, 45, and 230 pmol/min); AVE 0991 (45 pmol/min) combined with A-779 (180 pmol/min), or vehicle (6 microL/min). Baseline mean arterial pressure and heart rate were not altered during angiotensin(1-7) or AVE 0991 infusion. Angiotensin(1-7) (0.7 pmol/min) infusion produced a significant potentiation of the hypotensive effect of acetylcholine (3.1 ng: -9+/-1 mm Hg before; -18+/-2 mm Hg after; P<0.05). A similar potentiation was observed with the higher dose of angiotensin(1-7). As observed for angiotensin(1-7), infusion of AVE 0991 at 230 pmol/min potentiated the acetylcholine effect (3.1 ng: -8+/-2 mm Hg before; -16+/-2 mm Hg after; P<0.05). The potentiating effect was not observed for nitroprusside. A-779 or l-NAME treatment blocked the potentiation produced by angiotensin(1-7) or AVE 0991. Our data indicate that short-term stimulation of angiotensin(1-7) receptors improve endothelial function through facilitation of nitric oxide release. Topics: Acetylcholine; Angiotensin I; Angiotensin II; Animals; Blood Pressure; Dose-Response Relationship, Drug; Drug Synergism; Endothelium, Vascular; Enzyme Inhibitors; Hypotension; Imidazoles; Injections, Intravenous; Male; NG-Nitroarginine Methyl Ester; Peptide Fragments; Proto-Oncogene Mas; Proto-Oncogene Proteins; Rats; Rats, Wistar; Receptors, G-Protein-Coupled; Reference Values; Vasodilator Agents | 2005 |