John A. Czaja - US grants

Estrogens have wide ranging influences on the psychological and physiological health of women. Although linked to high blood pressure and cardiovascular disease, the locus and mechanisms of such actions on the cardiovascular system remain uncertain. In order to gather basic information on relationships between ovarian estrogens and blood pressure, an animal model was first developed which allows the direct computer collection of arterial blood pressures from conscious, unrestrained guinea pigs. It was found that a single injection of estradiol-17Beta, the most potent ovarian estrogen, rapidly and significantly lowered resting blood pressure and blunted the magnitude of pressor responses in response to intravenous infusions of norepinephrine, a chemical normally increased by stress. The estradiol treatment also significantly changed behavioral variables associated with fluid and mineral homeostasis. Two sets of experiments are therefore proposed to substantiate and extend these findings and to collect information on potential intervening variables. First, groups of instrumented animals will be injected with estradiol benzoate and/or progesterone for 6 days to assess whether blood pressure and vascular reactivity will remain depressed under more prolonged treatment and whether this depression can be blocked by the antiestrogenic actions of progesterone. Next, estradiol will be tested in long-term versus short-term ovariectomized females to evaluate whether prolonged hormone deprivation decreases or eliminates the cardiovascular effectiveness of estradiol. The major independent variables will be the levels of ovarian steroids as induced by peripheral injections. Dependent variables will include basal blood pressure, norepinephrine induced pressor responses, food and water intake, plus blood and urine osmolality. In order to evaluate whether the steroids may be acting directly on vasculature, aortas will be taken from animals as they complete their treatment protocols and used for in vitro experiments. These experiments are designed to measure the relative contractions to norepinephrine of aortic strips isolated from the steroid-treated subjects. By using appropriate animal and endocrine models, the proposed studies are aimed at clarifying the role of estrogens in cardiovascular homeostasis. My long-term objectives include determining the mechanisms by which ovarian steroids modulate cardiovascular parameters. Such basic information will hopefully help lead to more enlightened approaches to the surgical and pharmacological manipulations of female hormones.

biomedical equipment purchase;