ATTENUATED FOREARM VASODILATOR RESPONSE TO ATRIAL-NATRIURETIC-FACTOR IN THE ELDERLY

The vasodilator potency of human atrial natriuretic factor-(99-126) was investigated in the forearm vascular bed of 10 young and 10 elderly normotensive volunteers with venous occlusion strain gauge plethysmography. Atrial natriuretic factor was infused at six increasing dose steps into the brachial artery from 0.001 up to 0.3-mu-g/min/100 ml of forearm volume. This induced a mean +/- SEM increase in blood flow from 1.4 +/- 0.2 up to 6.0 +/- 1.0 ml/min/100 ml in the young and from 1.4 +/- 0.2 up to 3.9 +/- 0.6 ml/min/100 ml in the elderly. The dose-response curves of forearm blood flow and of forearm vascular resistance after increasing infusion rates of atrial natriuretic factor were shifted to the right in the elderly when compared with the young subjects. The mean percent decrease in forearm vascular resistance, induced by atrial natriuretic factor, during this dose-response curve averaged -31 +/- 3% in the elderly versus -56 +/- 3% in the young subjects (p = 0.0002). The calculated forearm spillover of the second messenger of atrial natriuretic factor, cyclic guanosine monophosphate, significantly increased from baseline values of 1.2 +/- 1.1 and 0.7 +/- 0.5 pmol/min/100 ml in young and elderly subjects, respectively, up to 23.2 +/- 5.0 and 30.5 +/- 7.0 pmol/min/100 ml during the highest dose of atrial natriuretic factor (both p < 0.01 versus baseline). There were no significant differences in the increments of the forearm spillover of this second messenger between both age groups. Further, both age groups demonstrated an equal vasodilator response to increasing infusion rates of the control vasodilator sodium nitroprusside, with a maximal decrease in forearm vascular resistance of 65 +/- 3% and 61 +/- 2% in the young and elderly group, respectively. This study demonstrates that advancing age in humans is accompanied by a specific reduction in vascular responsiveness to atrial natriuretic factor, without evidence for a diminished response of its second messenger. Therefore, we hypothesize that changes in postreceptor processes are involved in the age-related reduction in vascular sensitivity for atrial natriuretic factor.