EFLORNITHINE ALTERS CHANGES IN VASCULAR RESPONSIVENESS ASSOCIATED WITH COARCTATION HYPERTENSION

This study examined the temporal effects of the polyamine synthesis in hibitor eflornithine (alpha-difluoromethylornithine) on vascular respo nses to KCl, norepinephrine, sodium nitroprusside and acetylcholine in aortic rings from coarctation hypertensive rats. Coarctation hyperten sion reduced the contractile response of aortic rings to KCl and norep inephrine, increased sensitivity (reduced the EC(50) value) to norepin ephrine and attenuated relaxation to acetylcholine by 14 days of hyper tension. Treatment of coarctation hypertensive rats with eflornithine resulted in a normalization of the contractile intensity to KCl and no repinephrine and relaxations to acetylcholine by 14 days of hypertensi on. Responses to sodium nitroprusside were similar in all groups at al l time points. Hyperresponsiveness to norepinephrine produced by coarc tation of the aorta was not affected by eflornithine. These studies in dicate that normalization of vascular function can occur in the presen ce of significantly elevated blood pressure upon chronic administratio n of eflornithine. This functional normalization correlates with eflor nithine-mediated regression of structural abnormalities normally assoc iated with pressure overload hypertension.