CHARACTERIZATION OF THE RENAL MICROVASCULAR EFFECTS OF ANGIOTENSIN-II ANTAGONIST, DUP 753 - STUDIES IN ISOLATED PERFUSED HYDRONEPHROTIC KIDNEYS

被引：70

作者：

LOUTZENHISER, R ^{[1
]}

EPSTEIN, M ^{[1
]}

HAYASHI, K ^{[1
]}

TAKENAKA, T ^{[1
]}

FORSTER, H ^{[1
]}

机构：

[1] VET ADM MED CTR,NEPHROL SECT 111C1,1201 NW 16TH STREET,MIAMI,FL 33125

来源：

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

关键词：

ANGIOTENSIN-II; RENAL MICROCIRCULATION; AFFERENT ARTERIOLE; EFFERENT ARTERIOLE; RENAL HEMODYNAMICS;

D O I：

10.1093/ajh/4.4.309S

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

The renal microvascular effects of DuP 753, an orally active imidazole angiotensin II (ANG II) receptor antagonist were assessed directly in isolated perfused hydronephrotic rat kidneys. Unilateral hydronephrosis was induced to facilitate direct visualization of renal microvessels. Hydronephrotic kidneys were perfused in vitro and microvessel diameters were measured by automated computer-assisted image processing. The administration of 0.3 nmol/L ANG II decreased afferent arteriolar (AA) and efferent arteriolar (EA) diameters by 34 +/- 3% (from 17.9 +/- 0.6 to 11.9 +/- 0.6-mu-m, P < .001, n = 11) and 28 +/- 3% (from 17.1 +/- 1.3 to 12.3 +/- 1.3-mu-m, P < .001, n = 11), respectively. The subsequent administration of 0.1, 1.0, and 10-mu-mol/L DuP 753 reversed ANG II-induced vasoconstriction of the AA by 39 +/- 10%, 81 +/- 8%, and 103 +/- 9%, and of the EA by 22 +/- 7%, 51 +/- 6%, and 87 +/- 13%, respectively. These observations indicate that DuP 753 completely blocks both the renal afferent and efferent arteriolar actions of ANG II. In light of the pathogenetic role of ANG II in mediating the deranged renal hemodynamics associated with hypertension, conjestive heart failure, and some forms of renal insufficiency, our findings provide a theoretical framework for future studies assessing the potential therapeutic applicability of DuP 753 in reversing ANG II-mediated renal vasoconstriction.

引用

页码：S309 / S314

页数：6

共 45 条

[1] Symposium A., Physiological role of the intrarenal renin-angiotensin system, Fed Proc, 45, pp. 1411-1453, (1986)
[2] Debono E., Lee G.D., Mottram F.R., Et al., The action of angiotensin in man, Clin Sei Mol Med, 25, pp. 123-157, (1963)
[3] Furuyama T., Suzuki C., Shioji R., Saito H., Maebashi M., Aida M., Effect of angiotensin on renal function of the dog, Tohoku J Exp Med, 92, pp. 73-81, (1967)
[4] Aureli M., Renal response in man to plasma volume expansion and angiotensin, Scand J Clin Lab Invest, 24, pp. 1-59, (1969)
[5] Edwards R.M., Segmental effects of norepinephrine and angiotensin II on isolated renal microvessels, Am J Physiol, 244, pp. F526-F534, (1983)
[6] Casellas D., Carmines P.K., Navar L.G., Microvascular reactivity of in vitro blood perfused juxtamedullary nephrons from rats, Kidney Int, 28, pp. 752-759, (1985)
[7] Carmines P.K., Navar L.G., Disparate effects of calcium channel blockade on afferent and efferent arteriolar responses to angiotensin, Am J Physiol, 256, pp. F1015-F1020, (1989)
[8] Steinhausen M., Kucherer H., Parekh N., Angiotensin II control of the renal microcirculation: Effect of blockade by saralasin, Kidney Int, 30, pp. 56-61, (1986)
[9] Loutzenhiser R., Hayashi K., Epstein M., Calcium antagonists augment glomerular filtration rate of angiotensin II-vasoconstricted isolated perfused rat kidneys by dilating afferent but not efferent arterioles (Abst), J Cardio-Vasc Pharmacol, 12, (1988)
[10] Chiu A.T., Carini D.J., Johnson Al, et al: Nonpeptide angiotensin II receptor antagonists II. Pharmocology of S-8308, Eur J Pharmacol, 157, pp. 13-21, (1988)

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