The roles of V1a vasopressin receptors in blood pressure homeostasis: a review of studies on V1a receptor knockout mice.
A prompt rise in blood pressure occurs when arginine-vasopressin is administered in quantities adequate to activate vascular V1a subtype vasopressin receptors. However, it has been controversial whether the endogenous vasopressin-V1a system contributes to the maintenance of basal blood pressure during normal development and aging. Mutant mice lacking the V1a receptor gene (V1a(-/-)) show significantly lower blood pressure compared to control mice, without a notable change in heart rate. In V1a(-/-) mice, arterial baroreceptor reflexes were attenuated due to malfunctioning baroreflex center, and the mice's circulating blood volume was significantly reduced. In line with this reduction in circulating blood volume, adrenocortical hormone release was attenuated; plasma aldosterone levels were reduced and adrenocorticotropic hormone-stimulated corticosteroid release was attenuated. In addition, V1a receptor expression was detected in macula densa cells of the kidneys, which may have facilitated renin production from the juxtaglomerular cells. Deletion of the V1a receptor appears to impact the renin-angiotensin-aldosterone system. Studies on V1a(-/-) mice revealed that non-vascular V1a receptors in the central nervous system and peripheral tissues play critical roles in the maintenance of blood pressure homeostasis.
Division of Molecular Pharmacology, Department of Pharmacology, Jichi Medical University, 3311-1 Shimotsuke, Yakushiji, Tochigi, 329-0498, Japan.
Yoko
Y
Fujiwara
Akito
A
Tanoue
Gozoh
G
Tsujimoto
Taka-Aki
TA
Koshimizu
D000324:Adrenocorticotropic Hormone; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines / Q000627:therapeutic use; D001794:Blood Pressure / Q000502:physiology*; D001810:Blood Volume; D006333:Heart Failure; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007010:Hyponatremia / Q000188:drug therapy; D051379:Mice; D017483:Receptors, Vasopressin / Q000172:deficiency / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology
D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D017483:Receptors, Vasopressin; C106389:conivaptan; D000324:Adrenocorticotropic Hormone