Extracellular fluid volume is of critical importance to the regulation of arterial blood pressure. Recent studies from this laboratory and others have suggested that renal and adrenal responsiveness to angiotensin II is altered in essential hypertension. In approximately 40% of hypertensive patients, renal blood flow remains abnormally fixed in response to angiotensin II during changes in sodium balance state. These same 40% of patients with essential hypertension also have an adrenal abnormality, in which aldosterone responsiveness to angiotensin II is blunted during low sodium intake. These patients with abnormal renal and adrenal responses to angiotensin II with shifting sodium balance states have normal or high plasma renin activity. The renal and adrenal defects can be corrected by administration of converting-enzyme inhibitors. In addition, patients with low renin essential hypertension have been shown to have marked adrenal hyper-responsiveness to angiotensin II. Studies in our laboratory have been focused on the modulation of adrenal responsiveness to angiotensin II. Specifically, we have been interested in the role of dopamine in the modulation of aldosterone secretion. Our studies have shown that aldosterone secretion is under maximum tonic dopaminergic inhibition in normal human subjects.
We further have shown that dopamine blocks aldosterone responses to angiotensin II in sodium depleted individuals and inhibits by 80% aldosterone responses to upright posture without altering plasma renin activity. The inhibition of angiotensin II-induced aldosterone secretion by dopamine occurs only in the sodium-depleted state, and no effect is observed in individuals on normal sodium diet. Our studies indicate that the enhancement of aldosterone secretion in response to angiotensin II with low sodium intake may be accounted for by dopamine. Further, dopaminergic activity as measured by renal dopamine excretion is directly proportional to dietary sodium intake. On the basis of these studies, we hypothesize that reduced dopaminergic activity may be responsible for the path-ogenesis of low renin essential hypertension by two mechanisms. First, decreased dopaminergic activity leads to a direct increase in renal sodium excretion by hemodynamic and tubular mechanisms. Second, reduction in dopaminergic activity should increase aldosterone secretion and lead to expansion of extracellular fluid volume. The expansion of extracellular fluid volume by the renal and adrenal mechanisms together should suppress plasma renin activity and produce hypertension.