Close to a third of U.S. population is hypertensive and the health risk involved in hypertension grows with advancing age. The general treatment is antihypertensive (AHT) medication. Many, if not all, of these drugs can cause sexual dysfunction. Most of the literature provides only inadequate information on the nature, prevalence or mechanisms of action of this side effect, which often results in termination of treatment. This proposal contains four projects directed at increasing our knowledge and pays special attention to aging subjects. First, a prospective survey will be conducted evidence regarding several function of men aged 35-75 years, undergoing treatment with various antihypertensive drugs. Relationships between AHT medication, age, testosterone and prolactin levels, and other variables, will be explored. Second, an animal model will be used to determine if hypertension itself will affect sexual function in rats and what precisely are the sexual deficits resulting from the various types of AHT drug. Third, a pathophysiology of AHT drug- induced sexual dysfunction will be explored, using the animal model established in the previous project. Selective prototype AHT drugs will be studied to determine whether the deleterious effects on sexual function result from changes in contractility of genital smooth muscle or centrally, to affect neural regulation of sexual arousal and potency. Double-blind studies will be used to establish specific sexual effects of AHT drugs on men. These drugs will be chosen for their abilities to show similar effects in men and male rats, so that the study of the human pathophysiology can be guided by evidence from the rat models. Methodology, rats: Behavioral analysis of mating behavior and specific tests of component elements; pharmacologic manipulations; intrathecal, intracerebroventricular and cerebral micro-injections to locate actions of drugs in the nervous system; functional spinal transection by local application of anesthetics; hormone determinations and blood pressure measurements; and in vitro study of smooth muscle contractility using tissue baths. Methodology, humans: Psychometric, psychophysiological and psychophysical (sensory) testing; nocturnal penile tumescence measurements and prospective data keeping of components of sexual behavior.
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