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This study was performed to determine if an alteration in vascular polyamine contents is associated with the development of deoxycorticosterone acetate-salt hypertension. The effects of chronic administration of a-difluoromethylornithine, a specific irreversible inhibitor of ornithine decarboxylase and thus polyamine biosynthesis, on vascular polyamine contents, structure, and function as well as the development of hypertension was studied. Control and deoxycorticosterone acetate-salt rats received either tap water or a drinking solution containing or-difluoromethylornithine for 6 weeks, during which period systolic blood pressures were recorded. Vascular reactivity studies were performed on rings of aorta and tail artery. Medial thickness, vessel weight, and vascular polyamine contents were also assessed in these arteries. ar-Difluoromethylornithine treatment had no significant effect on either systolic blood pressure or vascular structure, function, and polyamine contents of control animals. The elevation in blood pressure and the increase in medial thickness, ring weight, and vascular polyamine contents as well as altered vascular reactivity observed in deoxycorticosterone acetate-salt rats was significantly attenuated by ar-difluoromethylornithine treatment These results are the first to demonstrate that vascular polyamine contents are elevated in the deoxycorticosterone acetate-salt rat and that chronic a-difluoromethylornithine treatment prevents the rise in vascular polyamines as well as the elevation in blood pressure and attendant changes in the vasculature. Thus, the increase in vascular polyamines may comprise a critical link between the initiating stimuli and the alterations in vascular structure and function implicated in the pathogenesis of deoxycorticosterone acetate-salt hypertension. (Hypertension 1991;18:85-92) P olyamines are found in all mammalian cells. 1 -3 A considerable body of evidence supports the view that these organic cations are essential for a number of cellular activities including growth, differentiation, and stimulus-response coupling involving transmembrane calcium fluxes.^ Ormthme decarboxylase (ODC), the initial and generally rate limiting enzyme involved in the biosynthesis of polyaminesti-3 is regulated by a variety of stimuli including neural and hormonal inputs.'.? Recent studies have suggested an important role for ODC or polyamines, or both, in various pathological conditions such as pulmonary and systemic hypertension.s-i* amine contents and thus, changes in the vasculature that contribute to an increase in peripheral vascular resistance. The present study was performed to determine if alterations in vascular polyamine content are associated with the development of DOCA-salt hypertension and the attendant changes in vascular structure and function. The effects of chronic administration of a-difluoromethylornithine (DFMO), a highly specific enzyme-activated irreversible inhibitor of ODC, 1 " 3 on vascular polyamine content, structure, and function as well as the deve...

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While a number of factors may initiate structural alterations within the cardiovascular system in response to hypertension, there are obligate cellular signaling mechanisms, such as the polyamines, through which they must operate. This study examined the effects of polyamine synthesis inhibition using eflornithine, a suicide inhibitor of ornithine decarboxylase on blood pressure, compensatory remodeling of the cardiovascular system, and cardiac and aortic polyamine contents using an aortic coarctation model in rats. Eflornithine treatment failed to reduce carotid arterial blood pressure and actually significantly elevated vascular pressure above and below the coarctation site by 14 days of hypertension. Eflornithine only transiently reduced aortic polyamine content of hypertensive rats while this agent reduced coarctation-induced aortic medial wall thickening and the synthesis/deposition of fibronectin and laminin in the hypertensive aorta. Increases in left ventricular mass and polyamine content were concomitantly reduced in hypertensive rats administered eflornithine. These results suggest that multiple polyamine regulatory pathways may maintain vascular polyamine content in response to aortic coarctation; however de novo polyamine synthesis is essential for select aspects of vascular remodeling, including matrix synthesis. Cardiac tissue, in contrast, may rely principally on de novo polyamine synthesis.