The experimental studies in this proposal are designed to determine if the higher amounts of plasma derived macromolecules which are found in arterial tissue in various models of hypertension in the rat are the result of increased transendothelial passage of plasma proteins and/or increased arterial tissue distribution space for macromolecules. The existing literature on the subject generally attributes the higher amounts of the macromolecular tracers accumulated after a given label circulation time to alterations in endothelial permeability. However, this conclusion is, in most cases, but one possibility among several equally viable speculations. The discrimination among the possibilities for this finding is of paramount importance in understanding and perhaps in treating the vascular disease which accompanies hypertension. The current proposal is to measure permeability and thoracic aorta (intima-media) steady state interstitial concentration for plasma albumin following in vivo circulation of the labeled protein. These measurements will allow the separation of the effects of altered permeability and those due to altered distribution space during (a) spontaneous hypertension in the rat. Additional studies will explore these same aortic properties during the administration of selected vasoactive compounds. Another group of expeiments will be performed on spontaneously hypertensive rats during the administration of the antihypertensive drugs alpha-methyldopa, minoxidil and hydralazine. These three drugs are of special interest due to their variable effects on reversal of the hypertension-induced increase in left ventricular weight inspite of the effectiveness of each in lowering blood pressure.