The long-term objectives of my research are to elucidate mechanisms of thermoregulatory control of the cardiovascular system during various forms of thermal stress, e.g., environmental temperature changes, febrile pyrogen reactions, etc. Previous studies have shown that the renal vasoconstriction inthe heat-stressed baboon is due primarily to activation of the renin-angiotensin (R-A) system by Beta-adrenergic mechanisms. The overall aim of this proposal is to elucidate further the mechanisms that produce renal vasoconstriction in the baboon during environmental heating (EH) and to determine various factors that may modify the renal vascular response to EH. Each baboon will be chronically instrumented with a flow probe around a renal artery, catheters for drug infusion and measuring arterial blood pressure, and a peri-arterial thermocouple for measuring core temperature (Tc). Each baboon will be subjected to EH experiments to raise Tc 2.5-3.0 degrees C within the context of the following specific aims and experimental protocols: (i) To determine the involvement of Alpha-adrenergic mechanisms in producing the rise in renal vascular resistance (RVR) during EH, EH will be applied to the baboon in normal and Alpha-receptor blocked states. (ii) To determine whether enhanced renal prostaglandin synthesis may be blunting the increase in RVR produced by renal vasoconstrictor stimuli during EH, EH will be applied to the baboon in normal and prostaglandin-blocked states. (iii) To determine whether the R-A system exerts its control on RVR during EH primarily by circulating or intrarenal angiotensin II, RVR changes in a surgically denervated kidney will be compared to that in the innervated kidney during EH. (iv) To determine whether states which change baseline R-A activity alter the magnitude of the RVR increase during EH, EH will be applied during states of chronic reduced sodium intake, chronic excess sodium intake, and acute saline loading. The RVR respones willk be compared to the normal respones during EH. (V) To determine whether hypohydration produced by water deprivation alters the RVR response to EH, EH will be applied to baboons in normal and hypohydrated states. These studies on the heat-stressed baboon, who has a unique control of the renal circulation by the R-A system, may provide insight into mechanisms controlling the renal circulation in man.
