The long term aim of this proposal is to define and characterize the specific intrarenal derangements in tubular and microcirculatory function that exist in the contralateral non-clipped kidney during the development and maintenance of hypertension induced by placement of a constriction around one renal artery (one clip, two kidney Goldblatt hypertension). Emphasis will be placed on the role of the increased activity of the renin-angiotension system that occurs as a consequence of the increased renin release by the clipped kidney. Since proximal tubular reabsorption in the contralateral kidney is decreased during inhibition of angiotensin converting enzyme, experiments will be conducted to determine the mechanism responsible for mediating this inhibition of tubular reabsorption. Studies will be designed to determine if the effects of converting enzyme inhibition are specifically due to blockade of angiotension II formation, and whether the elevated angiotensin II levels are enhancing proximal tubular reabsorption directly or indirectly by altering the peritubular capillary circulation and interstitial fluid environment. These experiments will be performed in anesthetized rats using micropuncture and microperfusion techniques. Using a recently developed """"""""in vitro"""""""" preparation that involves perfusion of individual juxtamedullary nephrovascular units that can be visualized directly, experiments will evaluate the specific alterations in functional capability of the afferent arterioles, glomerular capillaries, efferent arterioles and peritubular capillaries in this form of hypertension. Kidneys from rats clipped for 3 to 4 weeks will be studied with this method. To further quantitate the alterations in glomerular filtration rate and in interstitial and peritubular capillary dynamics in hypertension, studies utilizing the one clip, two kidney dog hypertensive model will be continued. These experiments will evaluate if the peritubular capillary or interstitial forces are readjusted during hypertension such that there is an enhanced net reabsorptive force that is inappropriate for the level of renal arterial pressure. The contribution of the elevated activity of the renin-angiotensin system will be determined in studies using inhibitors of the renin-angiotensin system.
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