EFFECT OF CONVERTING ENZYME-INHIBITION WITH SQ20,881 ON PLASMA AND URINARY KININS, PROSTAGLANDIN-E, AND ANGIOTENSIN-II IN HYPERTENSIVE MAN

被引:148
作者
VINCI, JM
HORWITZ, D
ZUSMAN, RM
PISANO, JJ
CATT, KJ
KEISER, HR
机构
[1] NHLBI, HYPERTENS ENDOCRINE BRANCH, BLDG 10, ROOM 7N258, BETHESDA, MD 20205 USA
[2] NIAMDD, REPROD RES BRANCH, BETHESDA, MD 20014 USA
关键词
Aldosterone; Angiotensin II; Bradykinin; Converting enzyme inhibition; Essential hypertension; Plasma renin activity; Prostaglandin E; Sq20.881;
D O I
10.1161/01.HYP.1.4.416
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
The relationship between levels of angiotensin II, kinins, and prostaglandin E and the depressor response to 1 or 3 mg/kg of the conrerting enzyme inhibitor SQ20.88I was studied in recumbent hypertensive subjects during 109 mEq and 9 mEq/day sodium intake. In 13 sodium-replete patients, SQ20,881 decreased angiotensin II from 46.7 ± 9.2 (mean ± SEM) to 31.7 ± 5.1 pg/ml and plasma aldosterone from 6.8 ± 0.9 to 2.9 ± 0.6 ng/dl (p < 0.003) without compensatory elevations of plasma renin activity and angiotensin I. Administration of SQ20.881 had no effect on plasma bradyklnin but it increased mean immunoreactive prostaglandin E from 143 ± 17 to 302 ± 75 pg/ml (p < 0.02) and in some patients it increased urinary kinin excretion. The distribution of the mean 2-hour depressor response was bimodal as four patients had a fall in diastollc pressure of at least 11 torr (mean 14 ± 1 torr) and nine had a minimal depressor response £ 4 torr, (-1 ± 1 torr); patients with a greater decrease in blood pressure showed an increase in urinary kinin excretion rate, whereas the other patients showed a fall (471 ± 121 vs - 99 ± 106 ng/hr; p < 0.005); both had similar control levels and responses of plasma angiotensin II, aldosterone, immunoreactive prostaglandin E, and brad} kinin. In nine sodium-depleted patients, SQ20.881 slightly decreased mean angiotensin II from 30.5 ± 4.5 to 22.4 ± 4.3 pg/ml early after drug administration, but because this was accompanied by rapid compensatory elevations of angiotensin I (which increased from < 14 pg/ml to levels as high as 513 pg/ml) and mean plasma renin activity from 43 ± 1.6 to 13.9 ± 43 ng/ml/hr, levels of angiotensin II returned toward control soon after drug administration. We found that SQ20381 had no effect on plasma bradykinin but increased urinary kinin excretion by 203 ± 63 ng/hr (p <0.02) and in some patients increased plasma prostaglandin E. The distribution of the mean 2-hour depressor response in these nine sodium-depleted patients was also bimodal as flve sodium-depleted patients had a depressor response to drug of at least 7 torr (10 ± 1 torr) while four sodium-depleted patients had a minimal response (-1 ± 1 torr). The patients with a greater decrease in blood pressure showed a greater (p < 0.05) increase in both immunoreactive prostaglandin E (248 ± 99 vs 20 ± 12 pg/ml) and urinary kinin excretion (270 ± 69 vs 83 ± 75 ng/hr) whereas decrements in plasma angiotensin II and aldosterone were similar. Thus, the depressor response to SQ20,881 correlated better with alterations in urinary kinins and plasma prostaglandin E than with changes in plasma levels of angiotensin II. © 1979 American Heart Association, Inc.
引用
收藏
页码:416 / 426
页数:11
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