The proposed research is designed to address four specific problems: (1) to establish the effect of arterial hypertension on the forces and membrane parameters governing fluid exchange across the microvascular walls in skeletal muscle (isolated, skinned rat hindquarters) in two experimental models of hypertension, spontaneously hypertensive (SHR) and two kidney, one clip hypertensive (RHR) rats, (2) to characterize the effect of acute arterial pressure alterations on the ability of skeletal muscle to autoregulate capillary hydrostatic pressure and transcapillary fluid exchange in these forms of hypertension, (3) to determine the role of Starling force readjustments in minimizing edema and also to quantitate changes in microvascular permeability in skeletal muscle subjected to total arterial inflow occlusion of varying duration and to assess humoral factors which may mediate the increased vascular permeability, and (4) to quantitate and determine the role of readjustments in Starling forces in minimizing edema formation in exercising skeletal muscle of normotensive and hypertensive rats. Microvascular permeability will be evaluated in all studies by determining the osmotic reflection coefficient for total plasma proteins. Capillary pressure will be determined by the venous occlusion technique, implanted capsules will be used to estimate interstitial fluid pressure, and plasma colloid osmotic pressure will be determined with a membrane osmometer. The capillary filtration coefficient and oxygen consumption will also be determined in order to more fully characterize transcapillary exchange during the pertubations outlined above. Hence, by studying the effect of the aforementioned conditions on capillary fluid exchange, we will be able to build a comprehensive model of the effect of different physiological and pathological states on fluid volume regulation in skeletal muscle.
