Increased oxidative stress diminishes NO‐mediated vasodilatation initiated by aldosterone in arterioles

There is increasing evidence that aldosterone has a significant impact on cardiovascular function. In the present study, we investigated direct vasoreactivity to aldosterone in resistance vessels. Mesenteric arterioles were isolated from normal Wistar rats and pressurized at 80 mmHg intravascular pressure in a no‐flow condition. Aldosterone (10 −12 to 10 −8 M) elicited a dose‐dependent vasodilator response, which was significantly inhibited by administration of spironolactone (10 −7 M), mineralocorticoid receptor antagonist, removal of the endothelium or inhibition of NO synthesis by Nω‐nitro‐L‐arginine methyl ester (3×10 −4 M). At a concentration of 10 −7 M, aldosterone elicited a reduced dilation, which was converted to a vasoconstriction after removal of the endothelium and a greater dilatation after scavenging superoxide with Tempol (10 −4 M) or inhibition of NAD(P)H‐oxidase with apocynin (10 −4 M). Intraluminal administration of aldosterone (10 −7 M) elicited a significantly greater and prolonged vasodilatation than extraluminal administration. These data suggest that the effects of aldosterone on resistance vessels depend on its concentration. In a physiological concentration, aldosterone increases arteriolar diameter via an endothelial NO‐mediated mechanism; however, in pathological concentrations, aldosterone increases oxidative stress, which may reduce NO bioavailability. (Supported by NIH HL‐43023, HL‐68813 and HL‐070653)