Regulation of Aldosterone Secretion

Williams, Gordon

Abstract

Since aldosterone modifies sodium homeostasis and indirectly vascular reactivity, understanding its regulation and derrangements there of may provide instight into the cause, and therefore, treatment or cure of certain diseases. Over the past three years we have reported that third of patients with essential hypertensio have an abnormality in the relationship between aldosterone and one of its regulatory factors, angiotensin II. Furthermore, we have suggested that his abnormality is etiologically related to the elevated blood pressure. Recently, we have documented that one form of genetic hypertension in rats appears to have a similar abnormality. Thus, our central hypothesis is that the Spontaneously Hypertensive Rat (SHR) is an excellent model for this subgroup of patients with essential hypertension. Therefore, understanding the cause of this biochemical abnormality and its relationship to the ypertension in SHR may provide inshight into the etiology of one form of human hypertension.
The specific aims are four fold: 1) to document that he SHR is an appropriate model fo this form of essential hypertension; 2) to determine the relationship between the biochemical abnormality and the development of the hypertension in SHR; 3) to assess whether the biochemical abnormality is secondary to a change in the adrenal - angiotensin II receptor, a modification of a post receptor event, or a chenge in the relative influence of other aldosterone regulatory factors; 4) to determine whether the abnormality in the adrenal-agiotensin II relationship applies to otherangiotensin II sensitive tissues, particularly the kidney. The procedures used will include in vitro studies using isolated, purified glomerulosa cells in which receptor binding and enzyme activity will be evaluated, and in vivo studies in both rat and man. The in vivo studies will examine angiotensin II's effect on the kidney and platelet as well as on the adrenal. From the data obtained, we will have a more clear understanding of the pathophysiology underlying one subset of patients with essential hypertension which should result in improved treatment and/or prevention.