ARGININE-VASOPRESSIN AND BAROREFLEX FUNCTION AFTER CONVERTING-ENZYME INHIBITION IN NORMAL HUMANS

Arginine vasopressin (AVP) has been shown to interact with sinoaortic and cardiac reflexes under selected experimental conditions. In humans , there is no evidence that AVP potentiates reflex function at modestl y increased plasma levels, except possibly if the angiotensin-converti ng enzyme (ACE) is inhibited. The objective of this study was to test the hypothesis that a modest physiological increase in plasma AVP woul d potentiate the responses of heart rate (HR), forearm vascular resist ance (FVR), plasma norepinephrine (NE), or systemic NE spillover to ba roreflex unloading and loading after pretreatment with lisinopril in h ealthy human volunteers. Seven normal young men were studied on three occasions. Baseline HR, FVR, and steady-state NE kinetics were establi shed, and AVP or vehicle (5% dextrose in water) was infused far 15 min double-blind on the first 2 days. Baroreflexes were then perturbed as follows: 15 min 60 degrees head-up tilt, 15 min 30 degrees head-down tilt plus 1,000 mi normal saline infusion, 15 min 30 degrees head-down tilt plus phenylephrine titrated to raise mean arterial pressure 10-1 5 mmHg. The study was repeated on a third day 12 h after 5 mg of lisin opril. Five additional subjects underwent similar baroreflex study on 2 days with only lisinopril and placebo. Before baroreflex deactivatio n and activation in the absence of lisinopril, AVP infusion had no hem odynamic or neurohormonal effects. During AVP infusion after lisinopri l, HR decreased from 67 +/- 6.5 to 62 +/- 4.5 beats/min (P < 0.05). AV P had no effect on the response of any variable during baroreflex pert urbation relative to vehicle, either with or without lisinopril. Lisin opril had no independent effect on these responses in the additional f ive subjects. At modestly increased plasma levels, AVP did not affect the responses of HR, FVR, plasma NE, or systemic NE spillover to baror eflex deactivation and activation. After lisinopril, AVP infusion prod uced a modest bradycardia but still had no significant positive effect on either response. These data suggest that inhibition of the angiote nsin-converting enzyme may unmask mild direct or vagally mediated effe cts of AVP on HR but does not unmask baroreflex potentiation.