A switch from GABA inhibition to excitation of vasopressin neurones exacerbates the development of angiotensin II-dependent hypertension

Abstract

Hypothalamic magnocellular neurones secrete vasopressin into the systemic circulation to maintain blood pressure by increasing renal water reabsorption, as well as by vasoconstriction. When blood pressure rises, baroreflex activation normally inhibits vasopressin neurones via activation of GABAergic inputs. However, plasma vasopressin levels are paradoxically elevated in several models of hypertension, as well as in some patients with essential hypertension, despite increased blood pressure. We have previously shown that vasopressin neurone activity is increased early in the development of moderate angiotensin II-dependent hypertension via blunted baroreflex inhibition of vasopressin neurones. In the present study, we show that antagonism of vasopressin-induced vasoconstriction slows the development of hypertension and that local administration of a GABAA receptor antagonist inhibits vasopressin neurones during, but not before, the onset of hypertension. Taken together, our data suggest that vasopressin exacerbates the increase in blood pressure evident early in the development hypertension and that blunted baroreflex inhibition of vasopressin neurones is underpinned by an excitatory shift in their response to endogenous GABA signalling.