Response of the kallikrein kinin and renin angiotensin systems to saline infusion and upright posture

Abstract

The possibility that bradykinin, a potent vasodilator, might be a physiological antagonist of the renin angiotensin system was investigated. 11 normal subjects, ranging in age from 21 to 33 yr were studied. Seven of the subjects were given a 10 meq sodium, 100 meq potassium, 2,500 ml isocaloric diet. After metabolic balance was achieved, they were infused with either 1 liter of 5% glucose over 2 hr or 2 liters of 0.9% saline over 4 hr. During the infusions, plasma renin activity (PRA), angiotensin II (A II), prekallikrein, bradykinin, and aldosterone levels were frequently determined. Plasma prekallikrein and kallikrein inhibitor did not change during the infusion of either glucose or saline. In subjects receiving saline, plasma bradykinin fell from 3.9±1.5 (SEM) ng/ml at 0 min to 0.93±0.2 at 30 min and 0.95±0.3 at 120 min. These changes paralleled the decrease in PRA over the same period (7.9±1.3 ng/ml/h to 5.6±0.8 at 30 min and 3.5±0.7 at 120 min). Similarly, A II fell from 113±12 pg/ml to 62±10 and 48±5, respectively, at 30 and 120 min. In contrast, the control group infused with glucose showed no change in bradykinin, A II, or PRA. Another four subjects were given a constant 200 meq sodium/100 meq potassium isocaloric diet. After metabolic balance was achieved, they were kept supine and fasting overnight. At 9 a.m. they assumed an upright position and began walking a fixed distance (200 ft) at a normal rate (3-4 ft/s). Plasma prekallikrein and kallikrein inhibitor did not change during the posture study. The plasma bradykinin rose from a base line of 0.54±0.01 (SEM) ng/ml to 0.96±0.13 at 20 min, 0.77±0.18 at 60 min, and 0.96±0.07 at 120 min. These changes parallel the increase in PRA over the same period (1.65±0.33 ng/ml hr to 3.6±0.85 at 20 min, 5.3±0.9 at 60 min, and 5.35±0.55 at 120 min). Likewise, the A II rose from 32.5±1.82 pg/ml to 50.8±3.6 at 20 min, 54.3±3.2 at 60 min, and 61.3±5.9 at 120 min. Thus, in sodium depleted individuals, saline infusion produces a rapid fall of plasma bradykinin at a rate similar to that observed for A II and PRA. Conversely, in sodium loaded individuals, assumption of upright posture leads to a parallel rise in A II, PRA, and bradykinin. These studies indicate that there is a close correlation of bradykinin levels with renin activity and angiotensin II, in both acute sodium loading and assumption of upright posture, suggesting that these two systems may be physiologically interrelated.