The objectives of this project are the following: (a) to determine the effect of age on the rate and extent of elevation of blood pressure in rats receiving an oral contraceptive chronically; (b) to determine the reversibility of the elevation of blood pressure in rats receiving an oral contraceptive chronically; (c) to assess in oral contraceptive-treated rats the level (receptor and/or beyond) at which the characteristically reduced Beta-adrenergic responsiveness may occur by: (1) testing the effect of inhibiting the phosphodiesterase enzyme and/or the adenosine inhibitory receptor on the reversibility of the reduced Beta-adrenergic responsiveness; (2) testing the responsiveness of isolated fat pads to isoproterenol with respect to release of cAMP and glycerol in order to determine whether any dissociation occurs between the two, and (3) determining the Beta-adrenoceptor number and affinity of cardiac tissue of oral contraceptive-treated rats; (d) to determine urinary output of catecholamines (epinephrine, norepinephrine, dopamine, and their metabolites) and sodium at rest and following a standardized stress of a 24 hour cold exposure (5 C.) so than an assessment of the effect of chronic treatment with an oral contraceptive on endogenous secretion and metabolism of catecholamines can be made. In addition, the relationship between urinary excretion of dopamine and sodium will be assessed in oral contraceptive-treated rats. (e) to determine whether chronic administration of a catecholestrogen, 2-hydroxyestradiol, the major metabolite of the most commonly used synthetic estrogenic agents, can elevate blood pressure and reduce the Beta-adrenergic responsiveness of rats. In addition, the responsiveness of endogenous secretion of catecholamines to cold stress will be assessed in catecholestrogen-treated rats.
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