Sympathetic Activity, Vascular Capacitance, and Long-Term Regulation of Arterial Pressure

Abstract

I am honored to have been chosen to present the 2008 Arthur C. Corcoran Memorial Lecture, because Dr Corcoran was both a brilliant scientist and one of the founding fathers in the field of hypertension research, but I am particularly gratified to join the list of superb scientists who have preceded me as Corcoran lecturers. When I began studying hypertension as a postdoctoral fellow, under the tutelage of Dr Michael Brody at the University of Iowa, I quickly acquired what turned out to be a lifelong interest in the integrative aspects of cardiovascular system regulation. Because of Dr Brody’s research interests, this naturally included a focus on the sympathetic nervous system. However, a major stimulus for my fascination with integrative physiology was the excitement at that time over the detailed and refined mathematical model of the circulation developed by Arthur Guyton, Thomas Coleman, and colleagues at the University of Mississippi.1 It is well known of course that the model highlights the importance of body fluid volume regulation as the key determinant of long-term arterial pressure regulation. The combined impact of these 2 influences—at a formative stage in my research career—led to my deep interest in the following question: “Can the sympathetic nervous system participate in long-term arterial pressure regulation within the framework of the Guyton-Coleman circulatory model?” Guyton and colleagues incorporated sympathetic regulation into their model. They emphasized the importance of nonrenal sympathetic activity in determining the hemodynamic pattern of many forms of hypertension and the potential for renal sympathetic nerve activity to affect the renal function curve (pressure-natriuresis relationship) and to thereby help establish the long-term value of arterial pressure. However, they also pointed out the tendency of reflex mechanisms regulating sympathetic activity to reset and, thus, maintain sympathetic activity at normal levels. This would minimize the influence …