This study investigated the effect of micropressure injection of the V1 arginine vasopressin (AVP) receptor antagonist into the area postrema on the ability of circulating AVP to augment baroreflex inhibition of renal sympathetic nerve activity (RSNA) in urethane-anesthetized rabbits. In addition, the effects of micropressure injections of AVP into the area postrema on RSNA, arterial pressure, heart rate, and baroreflex control of RSNA were evaluated. Injection of 100 ng (in a 10-nl volume) of

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... VP antagonist into the area postrema abolished the ability of AVP to enhance baroreflex inhibition of RSNA compared with phenylephrine (-8.84±0.89 before antagonist versus -4.83±0.44 %RSNA/mm Hg after antagonist). Normal baroreflex inhibition to phenylephrine (-3.95+±0.26 versus -4.10±0.33 %RSNA/mm Hg) was unaltered. This dose of AVP antagonist given intravenously or into the adjacent medial nucleus tractus solitarius was without effect. Micropressure injection of AVP directly into the area postrema produced a dose-dependent decrease in RSNA without significant effects on arterial pressure or heart rate. Local injection of 4±0.6 ng (in a 4-nl volume) of AVP produced an average 27±3% decrease in resting RSNA. Continuous injection of AVP into the area postrema using short-duration, low-frequency pressure pulses significantly augmented the baroreflex inhibition of RSNA during phenylephrine infusion (during AVP injection, -7.12±+1.60 %RSNA/mm Hg; control, -3.38+±0.55 %RSNA/mm Hg). These data support the hypothesis that circulating AVP acts at the area postrema to augment baroreflex inhibition of RSNA by a V1 receptor mechanism. (Circulation Research 1990;67:265-271) C irculating arginine vasopressin (AVP) interacts with arterial and cardiopulmonary baroreflexes to modulate reflex inhibitory effects on the sympathetic nervous system.'-4 When arterial pressure is elevated by infusions of AVP, the reflex inhibition of renal or lumbar sympathetic nerve activity is markedly greater than when pressure is raised by phenylephrine.4'5 In addition, elevations in plasma AVP concentration that exert minimal effects on resting arterial pressure, heart rate, or renal sympathetic nerve activity (RSNA) enhance the ability of the arterial and cardiopulmonary baroreflexes to inhibit RSNA in response to another pressor stimulus or in response to volume expansion.6X7 The ability of AVP to augment reflex inhibitory effects is eliminated by lesion of the area postrema, suggesting that the area postrema mediates the interaction of AVP with baroreflexes.4'6 Recent work also indicates that low-level electrical stimulation of the area postrema causes a current-and frequency-dependent inhibition of RSNA and significantly augments the baroreflex-mediated inhibition of RSNA in response to phenylephrine.8 Inhibition of sympathetic nerve activity can also be elicited by microinjection of glutamate directly into the area postrema.8 Previous work has also reported that reflexly or osmotically released AVP can modulate baroreflex control of the sympathetic nervous system.2'7'9 This interaction can be eliminated either by lesion of the area postrema or by intravenous administration of the specific V1 vasopressin receptor antagonist. Therefore, the present study was designed to evaluate the effects of