EFFECT OF AGE ON KINETICS OF NITRIC-OXIDE RELEASE IN RAT AORTA AND PULMONARY-ARTERY

Aging is an important determinant of vascular disease. Endothelium-der ived nitric oxide (NO) is protective as a vasodilator and inhibitor of platelet function, This study was designed to directly measure effect s of prolonged aging on endothelial MO release in isolated blood vesse ls and to delineate differences between the systemic and pulmonary cir culation. Aortas and pulmonary arteries from 5-6-mo-old (young), 18-19 -mo-old (middle-aged), and 32-33-mo-old (old) normotensive female rats were used, Blood pressure and plasma estradiol-17 beta (E(2)) remaine d unchanged. In isolated blood vessels, NO release was induced by the receptor-independent agonist calcium ionophore A23187 (10 mu mol/liter ) and measured in situ on the endothelial surface of vessels using a p orphyrinic microsensor, In vessels suspended in organ chambers isometr ic tension was recorded. Tn the aorta, the initial rate of NO release and peak NO concentration (sic) reduced in middle-aged and old rats (P < 0.0006 vs. young rats, n = 6), Furthermore, endothelium-dependent r elaxations to calcium ionophore and acetylcholine (both 10(-10)-10(-5) mol/liter) were also reduced in aortas from old as compared with youn g rats(n = 6, P < 0.05). The initial rate of NO release and peak NO co ncentration significantly correlated with maximal relaxation to calciu m ionophore A23187 (correlation coefficients r = 0.916, P < 0.0018 and r = 0.961, P < 0.0001, respectively, n = 7). In pulmonary arteries, h owever, the initial rate of NO release as well as peak No concentratio n did not decrease with age (n = 6 for each age group, NS). In both bl ood vessels, the NO release was unaffected by superoxide dismutase in all age groups (n = 6, NS). Thus, aging specifically reduces initial r ate and peak concentrations of endothelial NO release from aorta but n ot pulmonary artery indicating reduced NO production. As arterial pres sure did not change with aging, the chronic exposure of the aorta to h igher pressure and/or pulsatility than in the pulmonary artery may be the cause. This appears important as NO plays a protective role by pre venting vasoconstriction, thrombosis and atherosclerosis.