Age-Associated Endothelial Dysfunction in Rat Mesenteric Arteries: Roles of Calcium-Activated K+ Channels (Kca)

Abstract

Age-associated changes in large blood vessels were characterized by increased arterial wall thickness, luminal dilation and impaired endothelial function. But little is known about the effect of age on structural and functional changes in small resistance arteries. The mechanisms underlying age-associated endothelial dysfunction in rat mesenteric resistance arteries were investigated in the present study. Small rat mesenteric arteries were excised and cannulated, and vascular endothelial functions were tested by acetylcholine (ACh). Our experiments showed (1) endothelium-dependent vasorelaxation induced by ACh was reduced in aged mesenteric arteries; (2) blockade of K(ca) channels markedly reduced the vasodilation in young and adult rats, the resultant reduction in aged rats was much smaller compared with young and adult rats; (3) inhibition of endothelial nitric oxide synthase (NOS) resulted in a significant reduction of vasodilation in young and adult, but there was a smaller reduction in aged rats. The results suggest that (1) endothelial function was impaired in mesenteric arteries of aged rats; (2) both K(ca) channels and nitric oxide (NO) contribute together to the ACh-induced vasorelaxation in small mesenteric arteries, and (3) both the impairment of K(ca) channel function and decreased NO account for the age-related endothelial dysfunction.