Nitric oxide-dependent vasodilator mechanism is not impaired by hypertension but is diminished with aging in the rat aorta.

This study was designed to elucidate the effects of hypertension and aging on nitric oxide (NO)-mediated relaxation response to acetylcholine in the rat aorta. NO-mediated relaxation response was assessed as the relaxation response to acetylcholine after treatment with cyclooxygenase inhibitor in KCl-precontracted aortic rings. The endothelium-dependent relaxation responses to acetylcholine were lower in aortic rings isolated from spontaneously hypertensive rats (SHRs) at ages 16-20 and 55-60 weeks compared with those seen in agematched Wistar-Kyoto (WKY) rats. Aging induced a reduction of the relaxation response to acetylcholine in aortic rings from WKY rats but not from SHRs. Pretreatment with indomethacin enhanced the relaxation response to acetylcholine in only SHRs at ages 16-20 and 55-60 weeks, thereby cancelling the difference in the relaxation response between WKY rats and SHRs. Simultaneous administration of indomethacin and N G -nitro-L-arginine methyl ester abolished the relaxation response to acetylcholine in both strains. Thus NO-mediated relaxation response to acetylcholine was similar between WKY rats and SHRs at ages 16-20 and 55-60 weeks, respectively, and was attenuated with aging to the same degree in both strains. In conclusion, NO-mediated relaxation response to acetylcholine in the aorta is attenuated with aging but not impaired by hypertension.