Faria-Silva Raphael, Duarte Fernanda V, Santos Robson A S
Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Hypertension. 2005 Oct;46(4):948-52. doi: 10.1161/01.HYP.0000174594.17052.33. Epub 2005 Aug 8.
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.
在本研究中，我们评估了血管紧张素（1-7）及其非肽类似物AVE 0991对体内内皮功能的影响。实验在成年雄性清醒Wistar大鼠中进行，通过左颈动脉将聚乙烯导管植入降主动脉，用于注射乙酰胆碱或硝普钠，股动脉用于测量平均动脉压和心率；股静脉用于给药。在输注以下物质开始前及开始后30分钟，给予递增剂量的乙酰胆碱（3.1纳克至25.0纳克）或硝普钠（1.0微克至10.0微克）：血管紧张素（1-7）（0.7和7.0皮摩尔/分钟）；A-779（180皮摩尔/分钟）；血管紧张素（1-7）（7.0皮摩尔/分钟）与A-779（180皮摩尔/分钟）联合使用；AVE 0991（11、45和230皮摩尔/分钟）；AVE 0991（45皮摩尔/分钟）与A-779（180皮摩尔/分钟）联合使用，或溶剂（6微升/分钟）。在输注血管紧张素（1-7）或AVE 0991期间，基线平均动脉压和心率未改变。输注血管紧张素（1-7）（0.7皮摩尔/分钟）可显著增强乙酰胆碱的降压作用（3.1纳克：给药前-9±1毫米汞柱；给药后-18±2毫米汞柱；P<0.05）。较高剂量的血管紧张素（1-7）也观察到类似的增强作用。与血管紧张素（1-7）的情况一样，以230皮摩尔/分钟的剂量输注AVE 0991可增强乙酰胆碱的作用（3.1纳克：给药前-8±2毫米汞柱；给药后-16±2毫米汞柱；P<0.05）。硝普钠未观察到这种增强作用。A-779或L-NAME处理可阻断血管紧张素（1-7）或AVE 0991产生的增强作用。我们的数据表明，短期刺激血管紧张素（1-7）受体可通过促进一氧化氮释放来改善内皮功能。
