RESPONSES TO CONVERTING-ENZYME AND RENIN INHIBITION - ROLE OF ANGIOTENSIN-II IN HUMANS

We compared the renal vascular responses to angiotensin converting enz yme inhibition and renin inhibition to assess the influence of angiote nsin If (Ang II). We examined the renal and endocrine responses to the renin inhibitor enalkiren, to captopril, and to placebo in nine healt hy and nine hypertensive men on a 10-mmol sodium diet. Ang II was infu sed to assess effects of the agents on renal and adrenal responsivenes s to Ang II. Plasma Ang II concentration was suppressed similarly with enalkiren and captopril-an identical level of blockade was achieved. Although renal plasma flow was stable during placebo, a substantial ri se was seen with both enalkiren (+133+/-26 mL/min per 1.73 m(2)) and c aptopril (+99.4+/-22.6). There was remarkable intrasubject concordance between the renal plasma flow responses to renin inhibition and conve rting enzyme inhibition (r=.90, P<.004). The vasodilator response to b oth agents correlated inversely with the fall in renal plasma flow ind uced by Ang II alone (r= -.66, P<.05). Both agents significantly enhan ced the renal vascular response to Ang II (P=.01), and, furthermore, t he renal vasodilator response to captopril predicted the potentiation of the renal plasma flow response to Ang II after either agent (enalki ren: r=.91, P<.001; captopril: r=.56, P<.05). Concordance of the maxim al renal plasma flow response to the two agents appeared in the hypert ensive men as well. Our results indicate that the acute renal response to captopril largely reflects a reduction in Ang II formation. In hea lthy subjects, individual responses reflect differences in the extent to which Ang II contributes to renal vascular tone. Because difference s in neither plasma Ang II concentration nor renal or adrenal responsi veness to Ang II explain the individual variation, the data suggest a crucial variation in intrarenal Ang II concentration.