Vasopressin regulation of blood pressure and volume: findings from V1a receptor-deficient mice.
[Arg(8)]-vasopressin (AVP) has several functions via its three distinct receptors, V1a, V1b, and V2. The V1a vasopressin receptor (V1aR) is expressed in blood vessels and involved in vascular contraction. Recently, we generated V1a receptor-deficient (V1aR(-/-)) mice and found that they were hypotensive. In addition, V1aR(-/-) mice exhibited (1) blunted AVP-induced vasopressor response, (2) impaired arterial baroreceptor reflex, (3) decreased sympathetic nerve activity, and (4) decreased blood volume, all of which could contribute to the observed hypotension. In relation to their decreased blood volume, V1aR(-/-) mice had decreased plasma aldosterone levels, which could result not only from decreased activity of the renin-angiotensin system (RAS), but also from impaired AVP-stimulated aldosterone release in the adrenal glands. V1aR was found to specifically co-express at the macula densa cells with cyclooxygenase (COX)-2 and with neuronal nitric oxide synthase, which produces potent stimulators of renin, PGE(2), and NO. The expression levels of renin, COX-2, and nNOS were significantly decreased in V1aR(-/-) mice, which led to the suppression of RAS activity and consequent decreases in aldosterone and blood volume. Furthermore, V1aR is also expressed in collecting duct cells and involved in regulating water reabsorption by affecting V2/aquaporin 2 function. Thus, AVP regulates blood pressure and volume via V1aR by exerting diverse functions in vivo.
Aoyagi
Toshinori
T
Department of Pharmacology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
Koshimizu
Taka-aki
TA
Tanoue
Akito
A
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D001794:Blood Pressure; D001810:Blood Volume; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D017483:Receptors, Vasopressin / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000378:metabolism*
D017483:Receptors, Vasopressin; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin