Effect of combined V1a/V1b vasopressin receptor blockade within the paraventricular nucleus on neurocardiovascular responses (1130.2)

Abstract

The paraventricular nucleus (PVN) plays a critical role vasopressin (AVP) secretion by the neurohypophysis. AVP released from dendrites of magnocellular neurons within PVN influences systemic hemodynamics and renal sympathetic nerve activity (RSNA). Both V1a and V1b receptors exist on PVN neurons. We have shown that inhibition of either of these receptors alone blocks the rise in MAP and RSNA in response to AVP. We tested the hypothesis that combined subthreshold doses of V1a and V1b blockers within the PVN will inhibit AVP‐induced increases in MAP and RSNA. Studies were performed in awake, unrestrained,chronically instrmented male Sprague Dawley rats. Microinjection of 100 ng AVP into the PVN increased MAP 18.2±3.1 mmHg (P<0.001) while heart rate and RSNA decreased 52±21 bpm and 26.8±10.6%baseline, respectively (P<0.05). The response to combined subthreshold inhibitory doses of Manning compound (V1a, 20 ng) and nelivaptan (V1b, 0.5 ng) resulted in a significant attenuation of the rise in MAP, 13.3±3.2 mmHg, and attenuation of the reflex decrease in heart rate, 12±8 bpm, and RSNA, 7.2±4.6%baseline. Vehicle did not block any of the responses. These findings suggest that V1a and V1b activated pathways both participate and may interact to induce the pressor and sympathoexcitatory response to AVP within the PVN.Grant Funding Source: VA Merit Award