Husken_1994_Microvasc.Res_48_303

We have studied the effects of hypertension and aging on the concentration-response curves for alpha 1-adrenoceptor-mediated vasoconstriction and methacholine-induced endothelium-dependent relaxation. The experiments were performed in aortic rings and in perfused mesenteric vascular bed preparations taken from WKY rats, from SHR of 16-18, 28-30, and 58-60 weeks, and from 16- to 18-week-old SHRSP rats, respectively. The influence of aging and/or hypertension caused no alterations of the alpha 1-agonist response provoked by phenylephrine in aortic rings. Mesenteric vascular bed preparations showed an increase in maximal response to methoxamine when taken from hypertensive animals. Age per se did not change the contraction in the mesenteric arteries. Hypertension in combination with age caused a decrease in endothelium-dependent vasodilation induced by methacholine in aortic rings, but not in mesenteric arteries. However, the sensitivity to methacholine decreased age-dependently in the mesenteric vascular bed preparation taken from the WKY and SHR. The endothelium-independent relaxation induced by sodium nitroprusside showed a decrease in sensitivity in aortic rings taken from 58- to 60-week-old SHR when compared with the age-matched WKY. These findings suggest that the mechanisms beyond the endothelium involved in vasodilation are not responsible for the decreased methacholine-induced relaxation in aortic rings. It is concluded that (1) the responsiveness of resistance arteries to adrenoceptor stimulation only changes with elevated blood pressure and (2) hypertension in combination with aging induces an endothelial dysfunction in conduit arteries but not in resistance vessels.