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Abstract

The present invention provides a method for a more efficacious treatment of a vascular condition through the administration of a therapeutically effective amount of a combination of an anti-pressor agent, an endothelin antagonist, and a sex hormone for repetitive cycles of on/off-treatment. In one embodiment, the invention provides a method for the prevention of tolerance induced by an anti-pressor agent via the inclusion of an endothelin antagonist in a combination therapy approach to remodel vascular structure and treat vascular conditions associated with a male or female sexual dysfunction, atherosclerosis, renal failure, hypertension, congestive heart failure, diabetic nephropathy, and diabetic neuropathy. The anti-pressor agent comprises one or more compounds such as prostaglandin-E.sub.1, an ACE inhibitor, an angiotensin-II receptor antagonist, an .alpha..sub.1-adrenergic receptor antagonist, a .beta.-adrenergic receptor antagonist, a calcium channel blocker, an activator of guanylyl cyclase or adenyl cyclase, a phosphodiesterase inhibitor, and hydralazine. The endothelin antagonist comprises one or more compounds such as a peptidal endothelin antagonist, a non-peptidal endothelin antagonist, and an inhibitor of endothelin converting enzyme. Such a combination therapy approach enhances the efficacy of the anti-pressor agent and enables an increase in the frequency and duration of anti-pressor administrations for the long term treatment of vascular conditions.

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First Claim