Age-related decrease in endothelium-dependent dilator response to histamine in rat mesenteric artery.

The effect of aging on the vasodilator responses to histamine, 2-pyridylethylamine and 4-methylhistamine of ring segments of rat mesenteric arteries were investigated. The maximal extent of histamine-induced dilatation of the arteries previously contracted with norepinephrine was greatest for arteries from rats aged 2 and 8 weeks. The maximal response decreased progressively with an increase in age to 13 and 56 weeks. Arteries from 99 week old rats scarcely responded to histamine. Under these conditions, the dilatation induced by papaverine showed no change with age. The vasodilatation caused by 2-pyridylethylamine and 4-methylhistamine also decreased age dependently. The dilatation of the arteries induced by these agents was inhibited by the H1-antagonist chlorpheniramine, but not by the H2-antagonist cimetidine. Removal of the endothelium completely abolished the vasodilator effect of histamine, leaving the effect of papaverine unaffected. Hydroquinone and methylene blue reversed the dilatation induced by histamine, without affecting that caused by papaverine. These results suggest that the age-related decrease in dilatation of rat mesenteric artery in response to histamine is mainly due to a decrease in the ability of the endothelium to liberate a mediator(s).