Reduction of endothelial function with age in the mesenteric arterial bed of the normotensive rat.

1. Age-related changes in endothelial vasodilator function were studied in an in vitro preparation of the mesenteric arterial bed removed from male, normotensive, Wistar rats. 2. Animals were killed at 2, 12 or 22 months of age, the superior mesenteric artery was cannulated and the gut removed. The mesenteric arterial bed was perfused at a constant flow rate of 4 ml min-1 and perfusion pressure was taken as an index of arteriolar tone. 3. The muscarinic agonist, carbachol, antagonized noradrenaline-induced vasoconstriction in the presence, but not in the absence, of endothelium. This cholinoceptor agonist-induced release of endothelial-derived relaxing factor (EDRF) was impaired in 22 month old rats. 4. Noradrenaline-induced vasoconstriction increased following removal of endothelium suggesting that agonist-induced release of EDRF attenuates vasoconstrictor responses to noradrenaline measured in the presence of endothelium. 5. Removal of endothelium had less effect on noradrenaline-induced vasoconstriction in old rats suggesting once again that agonist-induced release of EDRF is impaired in old rats. 6. The noradrenaline dose-response curve established in the presence of endothelium was shifted to the left in 22 month old rats. 7. In conclusion, aging in the rat appears to lead to a reduction in endothelial vasodilator function in a resistance vessel.