ARE VASOPRESSIN PERIPHERAL V-1 RECEPTORS INVOLVED IN THE DEVELOPMENT OF MALIGNANT HYPERTENSION AND STROKE IN SHR-SPS

The aim of this study was to determine whether activation of vasopress in (AVP) peripheral V-1 receptors is involved in the development of ma lignant hypertension, stroke, and end-organ damage in stroke-prone spo ntaneously hypertensive rats (SHR-SPs). For this purpose, young salt-l oaded SHR-SPs were treated orally daily from their 5th to 34th week of age, by a selective AVP V-1 receptor antagonist, SR 49059, used in a dose (30 mg/kg) that achieved complete peripheral V-1 receptor blockad e. Untreated SHR-SPs served as controls. SR 49059 slightly and transie ntly (8th to 10th week of age) limited the rise in blood pressure, but thereafter systolic blood pressure values were similar in the two gro ups of SHR-SPs. Stroke-related mortality was not significantly differe nt in SR 49059-treated and in control animals (65% vs 65% at 30 weeks, 65% vs 83% at 34 weeks). SR 49059 did not prevent the increases in fl uid intake, diuresis and proteinuria seen in controls. Histological ex amination of the brain, kidneys and heart revealed that the developmen t of fibrinoid necrosis and arterial thickening was not prevented by S R 49059, nor was that of malignant nephroangiosclerosis and of myocard ial infarction and fibrosis. These data strongly suggest that AVP peri pheral V-1 receptor activation is not involved in the pathological pro cesses that develop in SHR-SPs.