It has been suggested that subtle humoral interactions may influence kidney function to enhance tubular reabsorption of fluid and electrolytes inappropriately in some types of hypertension. In essence, normal kidneys may respond appropriately to abnormally elevated levels of sodium- retaining hormones. Thus, inappropriate sodium conservation may result as a consequence of multiple and perhaps synergistic influences on various segments of the nephron. This project will specifically consider potential interactions between the reabsorptive influences of angiotensin II and catecholomines at the level of the proximal tubule. The basis for this approach is that hypertension in patients and/or experimental models has been associated with either elevated sympathetic neural activity or enhanced activity of the renin-angiotensin system or both. The main objectives of this project are to determine if angiotensin II and norepinephrine act in an additive or synergistic manner to enhance proximal tubule reabsorptive rate and to evaluate the cellular transport mechanisms mediating these effects. In accord with these objectives, we have the following specific aims: 1. To determine if, under in vivo experimental conditions, increases in peritubular concentrations of angiotensin II and norepinephrine above the endogenous levels exert synergistic effects on proximal tubule reabsorptive function. 2. To establish the effects of angiotensin II and norepinephrine, both individually and in combination, on proximal tubule reabsorptive function of the blood-perfused juxtamedullary nephron preparation. 3. To delineate the cellular mechanisms mediating the effects of angiotensin II and norepinephrine on proximal tubule cell transport function and determine if these mechanisms are interactive. These three main specific aims will be approach using three different experimental techniques: in vivo micropuncture and microperfusion, the blood-perfused juxtamedullary nephron preparation, and isolated proximal tubular cells.
Showing the most recent 10 out of 74 publications
