Contribution of endogenous vasopressin to regional hemodynamics in borderline-hypertensive Hiroshima rats.

Abstract

Inbred borderline-hypertensive Hiroshima rats (BHR) of the Wistar strain established in our laboratory are characterized by elevated plasma levels of vasopressin (Teranishi et al.: Jpn J Pharmacol 1999; 79: 251-255). To investigate the role of endogenous vasopressin in hypertension in BHR, we assessed the effect of a selective vasopressin V1 receptor antagonist (V1A) on regional hemodynamics using an electromagnetic flowmeter. The basal values of mean arterial pressure, heart rate, and regional resistances of renal and hindquarter vascular beds in conscious BHR were significantly higher than those in normotensive control rats (NCR). Injection of V1A (10 microg/kg) did not appreciably affect the hemodynamics in either animal. Successive administration of V1A after ganglionic blockade with hexamethonium bromide (C6; 25 mg/kg), however, significantly attenuated renal, mesenteric and hindquarter resistances in BHR but not in NCR. The hypotensive effect of V1A after sympathoinhibition was significantly greater in BHR than in both NCR and spontaneously hypertensive rats. However, the hypotensive effect induced by V1A was diminished only in BHR pretreated with a ganglionic blockade followed by injection of captopril (1 mg/kg). These findings indicate that BHR could be used as a new hypertensive model with an abnormality in endogenous vasopressin-mediated vasoconstriction appearing in the presence of angiotensin II after sympathoinhibition.