Increased resting tension abolishes endothelial anti-contractile effect induced by phenylephrine in renal hypertensive rat aorta

Abstract

The role of mechanical stress for vascular contraction is still unclear in hypertensive animals. This study aimed to evaluate the role of the rest tension of 1.5 g and 3.0 g on the endothelial nitric oxide synthase (eNOS) activity for contraction induced by the α1-adrenergic agonist phenylephrine (PE) in isolated intactendothelium aorta (E+) from renal hypertensive rat (2 K-1C) as compared to normotensive rat (2 K). Concentration-effect curves for PE were constructed in E+ under resting tension of 1.5 g or 3.0 g, in the absence or after incubation for 30 min with the NOS inhibitor (L-NAME 100 μM). The potency (pD2) and efficacy (ME) of PE were evaluated. eNOS residue Ser phosphorylation activates its enzyme. Phosphorylated Ser (P-Ser) expression was evaluated by Western Blot. This study was approved by the Ethics Committee of the University of Sao Paulo (156/2009). ME induced by PE on tension of 1.5 g was lower in 2 K-1C (1.2 ± 0.2 g, n = 7; p b 0.001) than in 2 K (2.2 ± 0.1 g; pD2:7.44 ± 0.03; n = 5), which was normalized by L-NAME. PE induced higher P-Ser-eNOS in 2 K-1C than in 2 K aorta. But under tension of 3.0 g, PE-induced contraction was similar in 2 K-1C and 2 K aorta. Therefore, these results indicate that the anti-contractile effect induced by PE in 2 K-1C E+ aorta under tension of 1.5 g is due to NO through eNOSSer phosphorylation that is abolished by the increased tension to 3.0 g. Supported by FAPESP, CNPq and CAPES.