Studies of the importance of atrial natriuretic peptides in physiology, pathophysiology and treatment in man
In this thesis an attempt has been made to try to dissect out the relative importance of atrial natriuretic peptides (ANP) and the renin-angiotensin-aldosterone system in the control of sodium balance in normal man. At the same time the thesis examines the relevance of ANP in the pathophysiology of essential hypertension and cardiac transplantation and the potential therapeutic value of manipulating the ANP system. The studies described in this thesis were important in suggesting a dominant role of suppression of the renin-angiotensin-aldosterone system in permitting excretion of short term increases in intravenous or oral sodium intake. The permissive effects of suppression of angiotensin II or aldosterone for the excretion of an intravenous sodium load showed clear time differences, with suppression of angiotensin II important immediately but the response to suppression of aldosterone delayed. In contrast, there appears to be only a transient role for changes in circulating levels of ANP in the response to an intravenous sodium load and little evidence that changes in ANP release are important in responding to acute increases in dietary sodium intake in normal subjects. However, the sensing mechanism for ANP release is clearly activated by sustained changes in dietary sodium intake. Studies of prolonged dietary sodium alteration in normal subjects clear evidence for a role of ANP in the medium term regulation of sodium balance and further dietary studies suggested an important role for the ANP system in pathophysiology in essential hypertension and in cardiac transplant recipients.