MULTIPLE POLYAMINE REGULATORY PATHWAYS CONTROL COMPENSATORY CARDIOVASCULAR HYPERTROPHY IN COARCTATION HYPERTENSION

While a number of factors may initiate structural alterations within t he cardiovascular system in response to hypertension, there are obliga te cellular signaling mechanisms, such as the polyamines, through whic h they must operate. This study examined the effects of polyamine synt hesis inhibition using eflornithine, a suicide inhibitor of ornithine decarboxylase on blood pressure compensatory remodeling of the cardiov ascular system, and cardiac and aortic polyamine contents using an aor tic coarctation model in rats. Eflornithine treatment failed to reduce carotid arterial blood pressure and actually significantly elevated v ascular pressure above and below the coarctation site by 14 days of hy pertension. Eflornithine only transiently reduced aortic polyamine con tent of hypertensive rats while this agent reduced coarctation-induced aortic medial wall and the synthesis/deposition of fibronectin and la minin in the hypertensive aorta. Increases in left ventricular mass an d polyamine content were concomitantly reduced in hypertensive rats ad ministered eflornithine. These results suggest that multiple polyamine regulatory pathways may maintain vascular polyamine content in respon se to aortic coarctation; however de novo polyamine synthesis is essen tial for select aspects of vascular remodeling, including matrix synth esis. Cardiac tissue, in contrast, may rely principally on de novo pol yamine synthesis.