Estimating renin participation in hypertension: Superiority of converting enzyme inhibitor over saralasin

• Published in: The American journal of medicine Vol. 61; no. 5; pp. 790 - 796
• Main Authors: Case, David B., Wallace, John M., Keim, Hans J., Weber, Michael A., Drayer, Jan I.M., White, Robert P., Sealey, Jean E., Laragh, John H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.1976
• Subjects: Adolescent; Adult; Angiotensin II - analogs & derivatives; Angiotensin II - physiology; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure - drug effects; Female; Humans; Hypertension - metabolism; Hypertension - physiopathology; Hypertension, Renal - physiopathology; Kidney Diseases - blood; Kidney Diseases - physiopathology; Male; Middle Aged; Oligopeptides - pharmacology; Renin - blood; Renin - physiology; Saralasin - pharmacology; Sodium - urine; Teprotide - pharmacology
• ISSN: 0002-9343; 1555-7162
• DOI: 10.1016/0002-9343(76)90160-1

This study was designed to examine more closely the differences in blood pressure responses in hypertensive patients to two agents which block the renin-angiotensin system. Accordingly, 39 seated patients received under the same conditions both saralasin, an octapeptide competitive antagonist of angiotensin II, and the nonapeptide converting enzyme inhibitor, SQ20881, which blocks the generation of angiotensin II from angiotensin I. A second component of the study involved administration of these agents in 10 additional studies in anephric subjects. Although both agents produced maximal responses in blood pressure that correlated well with each other (p < 0.001) and with the pretreatment plasma renin levels (p < 0.001), analysis of the results by renin subgroups revealed significant differences. Thus, both drugs lowered the diastolic pressures of patients with high renin levels, but converting enzyme inhibitor produced changes of greater amplitude (p < 0.05). In contrast, saralasin was consistently pressor in both patients with low renin levels and anephric patients in whom converting enzyme blockade produced no significant changes in blood pressure. Another impressive disparity in the responses to the two agents occurred in the group with normal renin levels in whom saralasin produced either neutral or pressor responses (mean change was +2.0 ± 1.5 standard error of the mean (SEM) per cent control diastolic pressure) whereas the converting enzyme inhibitor consistently induced depressor responses (mean change was −10.2 ± 1.2 per cent, p < 0.001). Altogether, the results suggest that converting enzyme inhibitor tests for angiotensin II-dependent blood pressure with more sensitivity than the partial agonist saralasin. Moreover, it is unlikely that the differences between the responses to the two agents were due to bradykinin accumulation, since depressor responses to converting enzyme inhibitor were not observed in the patients with low renin levels and the anephric patients.