Age-dependent decrease in endothelium-dependent hyperpolarizations to endothelin-3 in the rat mesenteric artery

The present study was designed to investigate the effects of age on the endothelium-dependent hyperpolarizing effect of endothelin-3 (ET-3) in the mesenteric artery of the rat. Main superior mesenteric arteries, with endothelium of young (7-9 weeks), adult (20-24 weeks), and old (40-50 weeks) male Wistar-Kyoto rats were studied. The cell membrane potential of the vascular smooth-muscle cells was measured with glass microelectrodes in the presence of indomethacin (inhibitor of cyclooxygenase) and NG-nitro-L-arginine (NLA, inhibitor of nitric oxide synthase). In preparations with endothelium from young rats, ET-3 produced transient hyperpolarizations in a concentration-dependent (10(-8) to 10(-9) M) manner. In tissues from adult rats, only a small hyperpolarization to the peptide was observed at 10(-7) M, whereas no detectable membrane potential changes were observed in tissues from old animals. In tissues of all groups, acetylcholine produced concentration-dependent hyperpolarizations, the maximal amplitude of hyperpolarization was reduced in the old rats but no significant differences were observed in the threshold concentration for hyperpolarization to acetylcholine. These data suggest that aging decreases endothelium-dependent hyperpolarizations evoked by both ET-3 and acetylcholine.