Skin blood flow increases and renal blood flow decreases in humans and baboons during environmental heating (EH). The proposed studies on baboons seek to elucidate (i) mechanisms by which body fluid volume reductions attenuate the cutaneous vasodilation (VD) during EH and (ii) the basic mechanisms that produce renal vasoconstriction (vc) during EH. Each baboon will be chronically instrumented with a flow probe around an external iliac artery or a renal artery, and catheters for infusions of drugs and solutions, blood sampling, and measurements of arterial blood pressure and core temperature (Tc). EH will consist of exposure to 38-42 degree C for 2-3 hours to raise Tc from sigma 37.0 to 39.5 degree C. The first two specific aims are to determine the importance of intravascular volume replenishment vs. intravascular + interstitial volume replenishment in removing the attenuation of the EH-produced cutaneous VD during dehydration (Aim #1) and administration of diuretics for 3 days (Aim #2). Dehydration will be produced by 64- 68 hours of oral fluid deprivation. The cutaneous VD during EH after intravascular replenishment by 6% dextran will be compared to that after intravAscular + interstitial replenishment by saline. These studies will give further insight into ways of ameliorating cardiovascular compromise in prolonged volume-depleted states. Three additional specific aims focus on the roles of the sympathetic nervous system (SNS) and renin-angiotensin system (RAS) in mediating renal VC during EH.
Aim #3 is to determine whether beta-adrenergic blockade completely blocks or just modestly attenuates the renal VC during EH, which type of beta-Adrenergic blockade (i.e., nonselective, beta 1 or beta 2) exerts this effect on renal VC, and whether the same beta-antagonists that modify renal VC also block activation of the RAS during EG.
Aim #4 is to determine whether the RAS contributes to the renal VC during EH by the vasoconstrictor action of angiotensin II or by modulating the renal VC produced by another mechanisms, such as the SNS. Studies will involve EH during inhibition of angiotensin I converting enzyme with and without simultaneous infusions of angiotensin II.
Aim #5 is to determine the importance of the SNS and its neural and circulating components in directly producing the renal VC during EH. Studies will include the effects renal denervation and pharmacologicAl blockades of neurotransmitter release and alpha- adrenergic receptors. These renal flow studies will enhance understanding of control of a vascular bed that may be involved in producing some forms of hypertension.
