EFFECTS OF DUP 753 ON PROXIMAL NEPHRON AND RENAL TRANSPORT

被引：20

作者：

COGAN, MG

XIE, MH

LIU, FY

WONG, PC

TIMMERMANS, PBMWM

机构：

[1] Nephrology Section (111J), Veterans Administration Medical Center, San Francisco, CA, 94121

来源：

AMERICAN JOURNAL OF HYPERTENSION | 1991年 / 4卷 / 04期

关键词：

ANGIOTENSIN-II RECEPTOR ANTAGONIST; RENAL TRANSPORT; CAPTOPRIL; FREE-FLOW MICROPUNCTURE AND CLEARANCE TECHNIQUES;

D O I：

10.1093/ajh/4.4.315S

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

We used the nonpeptide angiotensin II receptor antagonist DuP 753, which lacks the agonist and kinin/prostaglandin-inducing properties of saralasin and captopril, respectively, to examine the role of endogenous angiotensin II in regulating transport in the proximal convoluted tubule (PCT) and whole kidney. During in vivo microperfusion in the Munich-Wistar rat, a maximally effective dose of DuP 753 (10 mg/kg, intravenously) powerfully inhibited absorption of bicarbonate (370 +/- 3 to 200 +/- 9 pEq/mm.min, P < .001), chloride (214 +/- 3 to 105 +/- 9 pEq/mm.min, P < .001), and water 5.2 +/- 0.1 to 2.8 +/- 0.2 nL/mm.min, P < .001) in the S1 subsegment of the PCT. DuP 753 was significantly more effective than captopril (3 mg/kg, intravenously) in inhibiting sodium chloride transport and is the most potent diuretic ever described in this segment. Consistent with the axial decline of angiotensin II receptor density in the PCT, DuP 753 was a less effective transport inhibitor in the S2 subsegment of the PCT, similar to captopril. Using free-flow micropuncture and clearance techniques, though inhibition in the earliest segment of the nephron is partially compensated by downstream reabsorption, DuP 753 induces a substantial diuresis, natriuresis, and chloruresis. In conclusion, DuP 753 markedly decreases S1 PCT fluid and electrolyte absorption, indicating that endogenous angiotensin II exerts significant tonic support of proximal transport in vivo.

引用

页码：S315 / S320

页数：6

共 22 条

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