Existing evidence suggests that vasopressin (VP, antidiuretic hormone) release is elevated in several types of experimental hypertension as well as in humans with hypertension. Furthermore, the VP system is hyperresponsive to certain stimuli in rats genetically disposed to spontaneous development of hypertension (e.g. the spontaneously hypertensive rats (SHRs) developed by Okamoto) but relationships between this hyperresponsiveness and the hypertension is unclear. Therefore, experiments are proposed to evaluate this relationship. Two approaches will be used:

1). The importance of the hyperresponsiveness to the development of hypertension will be evaluated by chronically blocking the vasopressin effects of VP with an analog of VP which has specific pressor antagonist actions. Similarly the contribution of elevated VP release to the maintenance of blood pressure at the different stages of the hypertensive process will be analyzed by acutely infusing the VP pressor antagonist during the development and chronic phases of hypertension.

2). The opposite relationship also will be examined, e.g. the potential role of the hypertension in initiating the hyperresponsiveness of the VP system or in the eventual disappearance of the hyperresponsiveness. This will be evaluated by using three interventions to prevent development of the hypertension and examining the responsiveness of the VP system in rats with these interventions. The interventions employed will be chronic converting enzyme inhibition, intraventricular 6-hydroxydopamine injections, and renal denervation. In rats maintained normotensive with some of these interventions, the responsiveness of the renin-angiotensin system and the NE innervation of VP neurons also will be evaluated, because abnormalities in these factors have also been observed in SHRs.

R01HL028172

1982-01-01

1988-06-30