Nitric oxide-mediated dilation of arterioles to intraluminal administration of aldosterone.

The nature of the rapid action of aldosterone on blood vessels, whether endothelium-dependent dilation or smooth muscle-dependent constriction is predominant, is still in dispute. In this study, we administered aldosterone intraluminally or extraluminally to isolated mesenteric and cerebral arterioles of male Wistar rats. Extraluminal administration of aldosterone (10(-11) or 10(-7) M) elicited a transient vasodilatation. The peak response appeared at approximately 5 minutes. In contrast, intraluminal administration of aldosterone elicited a greater and sustained dilation. When aldosterone (10(-12)-10(-7) M) was administered extraluminally in a cumulative manner, dose-dependent vasodilator responses were elicited, except a reduced dilation was observed to 10(-7) M aldosterone. The dilations were significantly inhibited by spironolactone (10(-7) M), a mineralocorticoid receptor antagonist or Nomega-nitro-l-arginine methyl ester (3 x 10(-4) M), a NO synthesis inhibitor. In endothelium-denuded vessels, extraluminal aldosterone induced a dose-dependent vasoconstrictor response. Scavenging superoxide with Tempol (10(-4) M) sustained the extraluminal aldosterone (10(-11) or 10(-7) M)-induced dilation, whereas inhibition of NO synthesis or removal of the endothelium abolished intraluminal aldosterone-induced dilation. Dilation to 10(-7) M aldosterone was significantly enhanced after inhibition of NAD(P)H-oxidase with apocynin (10(-5) M). Furthermore, in the presence of endothelial dysfunction, induced by chronic inhibition of NO synthesis, intraluminal administration of aldosterone failed to dilate the arterioles. We conclude that in physiological conditions, acute elevation of aldosterone will evoke mainly an endothelium-dependent NO-mediated dilation.

Effects of n-3 fatty acids and acute exercise on endothelium-dependent vasorelaxation in healthy rat aorta.

The purpose of this study was to determine whether n-3 PUFA result in an effect on endothelial function that is in addition to that of acute exercise. For 4 weeks, male Sprague-Dawley rats were subjected to a diet based on n-3 PUFA or a standard diet. In each diet group, ten rats were submitted to an acute treadmill exercise while the remaining ten acted as sedentary controls. The running speed was progressively increased until the animals were exhausted. Endothelial function was then assessed by measuring isometric tension in rings of the thoracic aorta. In vessels precontracted with 0.1 microm-phenylephrine, responses to acetylcholine (ACh) were significantly improved following acute exercise in all diet groups. When PUFA supplementation was compared to the standard diet no significant difference was found in response to ACh, either at rest or after an acute exercise. Pretreatment of rings with Nomega-nitro-l-arginine methyl esther (50 microm) inhibited the ACh-mediated vasorelaxation in all groups. Response to 10 microm-nifedipine, an L-type Ca2+ channel antagonist, was similarly enhanced after acute exercise in both standard and PUFA diets. Furthermore, response to 0.01 microm-nifedipine was significantly higher after acute exercise only in the PUFA diet. In conclusion, in our 'healthy' rat model with 'normal' baseline endothelial function, acute exercise improves response to ACh while PUFA supplementation alone or in combination with acute exercise has no effect on endothelium-dependent vasorelaxation. However, PUFA may potentiate the acute exercise effect on smooth muscle cell relaxation via L-type Ca2+ channel modifications.

Effect of training frequency on endothelium-dependent vasorelaxation in rats.

BACKGROUND: Moderate physical activity enhances endothelium-dependent vasorelaxation. Whether the frequency of exercise affects endothelial function is unclear. The purpose of this study was to investigate the effects of various frequencies of training on endothelium-dependent vasorelaxation. DESIGN: Male Wistar rats were trained for 8 weeks on a treadmill at various frequencies [1 (Ex1), 3 (Ex3) or 5 days/week (Ex5)] and compared with age-matched sedentary animals (SED). A control group allowed us to assess endothelial function before the exercise protocol. Rings of thoracic aorta were precontracted with phenylephrine. RESULTS: Endothelium-independent relaxation elicited by sodium nitroprusside was similar in all groups. The maximal response elicited by acetylcholine (ACh) was not different between groups, whereas pD2 values (-logEC50, EC50 being the concentration of ACh that elicited 50% of the maximal response) significantly correlated with frequency of training. nitro-L-arginine methyl ester (L-NAME) reduced the relaxation elicited by 10(-7) mol/l ACh or higher in control and all trained groups, and by 10(-6) mol/l ACh or higher in SED group. Indomethacin inhibited the vasodilating response to 10(-7) mol/l ACh or higher in control, SED and Ex1 groups, and to 10(-8) mol/l or more in Ex3 and Ex5 animals. Tetraethylammonium attenuated the response to 10(-6) mol/l ACh or higher in control and SED groups and to 10(-7) mol/l or more in all trained animals. CONCLUSION: This data suggest that decreased ACh-induced vasorelaxation after physical inactivity may result from impairment of endothelial nitric oxide synthase, prostacyclin and endothelium-derived hyperpolarizing factor pathways. This effect is prevented by training in a frequency-dependent manner.