Endogenous Angiotensin II as a Determinant of Sodium-Modulated Changes in Tissue Responsiveness to Angiotensin II in Normal Man*

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Abstract
Dietary sodium restriction reduces vascular smooth muscle, particularly renovascular, responsiveness to infused angiotensin II (All), while the responsiveness of the adrenal and the All-renin short feedback loop to All is enhanced. To determine whether circulating All mediates these changes in responsiveness, we studied 11 sodium-restricted and 9 sodiumreplete 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 All infusion (0.3–10 ng/kg·min) before and after MK421 administration. Plasma aldosterone, cortisol, PRA, All, sodium, potassium, and PAH clearance were measured at the onset and end of each All dose. In sodium-restricted subjects, preinfusion All and aldosterone levels were significantly reduced, (P < 0.001) to the range found in sodium-replete subjects, after 75 h of MK421 administration, whereas blood pressure and PAH responses to infused All were significantly enhanced (P < 0.01). Blood pressure and PAH responses to infused All 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 All infusion were similar before and after MK421 on both diets. Thus, sodium-modulated changes in PAH and blood pressure responsiveness to infused All depend on circulating All levels. However, circulating All does not mediate sodium modulation of adrenal or PRA short-feedback loop responsiveness to infused AIL Two different mechanisms determine sodium modulation of tissue responsiveness to AH; in one, circulating All via a receptor mechanism is the mediator, and in the other, some other factor(s) also linked to sodium intake must be responsible.