Endogenous angiotensin II as a determinant of sodium-modulated changes in tissue responsiveness to angiotensin II in normal man.
Dietary sodium restriction reduces vascular smooth muscle, particularly renovascular, responsiveness to infused angiotensin II (AII), while the responsiveness of the adrenal and the AII-renin short feedback loop to AII is enhanced. To determine whether circulating AII mediates these changes in responsiveness, we studied 11 sodium-restricted and 9 sodium-replete normal subjects before and after 75 h of converting enzyme inhibitor pretreatment with MK421. All subjects received infusions of paraaminohippurate (PAH) to assess renal plasma flow during graded AII infusion (0.3-10 ng/kg X min) before and after MK421 administration. Plasma aldosterone, cortisol, PRA, AII, sodium, potassium, and PAH clearance were measured at the onset and end of each AII dose. In sodium-restricted subjects, preinfusion AII and aldosterone levels were significantly reduced, (P less than 0.001) to the range found in sodium-replete subjects, after 75 h of MK421 administration, whereas blood pressure and PAH responses to infused AII were significantly enhanced (P less than 0.01). Blood pressure and PAH responses to infused AII in sodium-replete subjects were not significantly modified by MK421 treatment, confirming that the drug effect was specific. In contrast, the plasma aldosterone increment and PRA decrement after AII infusion were similar before and after MK421 on both diets. Thus, sodium-modulated changes in PAH and blood pressure responsiveness to infused AII depend on circulating AII levels. However, circulating AII does not mediate sodium modulation of adrenal or PRA short-feedback loop responsiveness to infused AII. Two different mechanisms determine sodium modulation of tissue responsiveness to AII; in one, circulating AII via a receptor mechanism is the mediator, and in the other, some other factor(s) also linked to sodium intake must be responsible.
D000293:Adolescent; D000328:Adult; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood*; D001794:Blood Pressure / Q000187:drug effects; D004039:Diet, Sodium-Restricted; D004151:Dipeptides / Q000494:pharmacology*; D004656:Enalapril; D005260:Female; D006801:Humans; D007668:Kidney / Q000098:blood supply; D008297:Male; D008875:Middle Aged; D012039:Regional Blood Flow / Q000187:drug effects; D012083:Renin / Q000097:blood; D010130:p-Aminohippuric Acid / Q000494:pharmacology
D004151:Dipeptides; D000804:Angiotensin II; D000450:Aldosterone; D004656:Enalapril; D012083:Renin; D010130:p-Aminohippuric Acid