V1a vasopressin receptors maintain normal blood pressure by regulating circulating blood volume and baroreflex sensitivity

Abstract

Arginine-vasopressin (AVP) is a hormone that is essential for both osmotic and cardiovascular homeostasis, and exerts important physiological regulation through three distinct receptors, V1a, V1b, and V2. Although AVP is used clinically as a potent vasoconstrictor (V1a receptor-mediated) in patients with circulatory shock, the physiological role of vasopressin V1a receptors in blood pressure (BP) homeostasis is ill-defined. In this study, we investigated the functional roles of the V1a receptor in cardiovascular homeostasis using gene targeting. The basal BP of conscious mutant mice lacking the V1a receptor gene (V1a ؊/؊ ) was significantly (P < 0.001) lower compared to the wild-type mice (V1a ؉/؉ ) without a notable change in heart rate. There was no significant alteration in cardiac functions as assessed by echocardiogram in the mutant mice. AVP-induced vasopressor responses were abolished in the mutant mice; rather, AVP caused a decrease in BP, which occurred in part through V2 receptor-mediated release of nitric oxide from the vascular endothelium. Arterial baroreceptor reflexes were markedly impaired in mutant mice, consistent with a loss of V1a receptors in the central area of baroreflex control. Notably, mutant mice showed a significant 9% reduction in circulating blood volume. Furthermore, mutant mice had normal plasma AVP levels and a normal AVP secretory response, but had significantly lower adrenocortical responsiveness to adrenocorticotropic hormone. Taken together, these results indicate that the V1a receptor plays an important role in normal resting arterial BP regulation mainly by its regulation of circulating blood volume and baroreflex sensitivity.knockout mouse ͉ adrenal cortex T he neurohypophyseal hormone arginine vasopressin (AVP) is involved in a plethora of physiological regulatory processes that occur via stimulation of specific V1a, V1b, and V2 receptors (1). These receptors have distinct pharmacological profiles and couple with specific intracellular second messengers (1). Vasopressin plays a prominent role in the cardiovascular system and influences arterial blood pressure (BP) at multiple sites in a complex fashion. The role of AVP has been well characterized in the regulation of BP in pathophysiological conditions such as severe hypovolemia͞hypotension episodes (2). However, its contribution to BP homeostasis in normal physiological situations is ill-defined (3). Vasopressin is a potent stimulator of vascular smooth muscle contraction in vitro, and V1a receptors mediate its vasoconstrictor effect (3). However, a relatively large amount of vasopressin is required to raise BP in vivo under normal physiological conditions (4); this is thought to be because vasopressin also acts on the brain, decreasing cardiac output by inhibiting sympathetic efferent activity and potentiating baroreflexes (5). AVP has been shown to enhance baroreflex function via activation of V1 receptors in the area postrema (6-8). In addition, vasopressin causes vasodilatation in some blood vessels, perhaps via rele...

Vasopressin Stimulates Na-dependent Phosphate Transport and Calcification in Rat Aortic Smooth Muscle Cells

“…Among them, AVP is known to be a potent vasoconstrictor that stimulates the proliferation of VSMC [12,13,18]. While three receptor subtypes exist for AVP (V1a, V1b and V2), V1a receptor has been reported to play the dominant role in cardiovascular system and behavior [41,42]. It has recently been reported that V1a-/-mice showed lower blood pressure through the reduction of blood volume and the impairment of the baroreceptor reflex [42].…”

“…While three receptor subtypes exist for AVP (V1a, V1b and V2), V1a receptor has been reported to play the dominant role in cardiovascular system and behavior [41,42]. It has recently been reported that V1a-/-mice showed lower blood pressure through the reduction of blood volume and the impairment of the baroreceptor reflex [42]. On the other hand, V1b-/-mice have been reported to show mildly impaired social recognition [43], but so far little information is provided on cardiovascular disorder in V1b-/-mice.…”

Hypothalamic-pituitary-adrenal axis function during perinatal depression

“…The first involves the hypothalamic magnocellular acting through its peripheral cognate V1a receptor [49,50] , a G-protein-coupled receptor signaling via phospholipase C [51][52] , is largely responsible for regulating water homeostasis and blood pressure [49,53] . The second system consists of parvocellular neurons within the PVN; these neurons produce both AVP and CRH peptide hormones [55] .…”

Sodium Excretion in Response to Vasopressin and Selective Vasopressin Receptor Antagonists

“…58 (4) Interestingly, mice with deletion of the V1aR exhibit a lower BP as a result not of a reduced vasoconstriction but of a lower extracellular fluid volume. 59 In summary, these results provide a better knowledge of the respective V2R-and V1aR-dependent effects of AVP on sodium excretion in rats. Whether a similar balance between V1aR-and V2R-dependent effects occurs in humans remains to be determined.…”