SPONTANEOUS HYPERTENSION: EFFECTS OF EARLY ENVIRONMENT

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The experiments described in this proposal will evaluate the role of the early maternal environment in the development of sympathetic nervous system hyperreactivity and elevated blood pressure in the spontaneously hypertensive (SHR) rat, an animal model of human essential hypertension. Our experimental approach will involve altering the early maternal environment of SHR and Wistar-Kyoto (WKY) normotensive litters by reciprocal cross-fostering and examining the effects of this treatment on the development of sympathetic-adrenal medullary activity and behavior of rats while undisturbed and during acute exposure to stressful stimulation. Specifically, SHR and WKY litters will be reared under 1 of 3 conditions: (a) control- rearing of the litter by the natural mother; (b) in-fostered- rearing of the litter by a foster mother of the same strain; or (c) cross-fostered- rearing of the litter by a foster mother of the opposite strain. With additional control groups of SHR and WKY litters, we will determine if the effects of the maternal environment on sympathetic activity and hypertension are mediated by strain differences in maternal behavior or by a hypertensinogen transmitted through the milk. To assess the effects of the maternal environment on the development of the sympathetic-adrenal medullary system, rats of the 6 strain-treatment groups (ages 2,4,8,12,16, or 20 days) will be injected with saline or insulin and sarcrificed 3 hours later. The induction of ornithine decarboxylase in heart and the depletion of epinephrine from the adrenal medulla will serve as markers of tissue responses to insulin-induced sympathetic stimulation. In addition, we will test SHR and WKY male rats at 6, 12 or 18 weeks of age to determine possible long term effects of the maternal environment on behavioral and physiological responses. For rats at each age, we will measure open field behavior and basal values of heart rate, mean blood pressure and plasma levels of nerepinephrine and epinephrine and changes in each of the above parameters following acute exposure to intermittent footshock. The results of this research will provide important information regarding the impact of the preweaning maternal environment on the development of the sympathetic-adrenal medullary system in genetically hypertensive and normotensive rats. Further, our studies will clarify in post-weaned SHR rats the significance of sympathetic hyperresponsiveness during acute stress as a risk factor for the development of hypertension.