PROLONGED ENDOTHELIN BLOCKADE PREVENTS HYPERTENSION AND CARDIAC-HYPERTROPHY IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

被引：45

作者：

STASCH, JP

HIRTHDIETRICH, C

FROBEL, K

WEGNER, M

机构：

[1] Cardiovascular and Arteriosclerosis Research, Bayer AG, Wuppertal

[2] Institute for Chemistry, Bayer AG, Wuppertal

来源：

AMERICAN JOURNAL OF HYPERTENSION | 1995年 / 8卷 / 11期

关键词：

ET(A)-RECEPTOR ANTAGONIST; STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS; HYPERTENSION; ATRIAL NATRIURETIC PEPTIDE; PLASMA RENIN ACTIVITY; FR; 139317;

D O I：

10.1016/0895-7061(95)00224-D

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

The cardiovascular consequences of endothelin (ET) blockade with the ET(A)-receptor antagonist FR 139317 were evaluated by determining the long-term effects of the drug on hemodynamic, hormonal, renal and structural parameters in stroke-prone spontaneously hypertensive rats (SHR-SP). Young SHR-SP on a high-sodium diet develop malignant hypertension accompanied by renovascular and cerebrovascular lesions. In control SHR-SP the systolic blood pressure increased from 196 +/- 3 to 260 +/- 4 mm Hg, whereas in animals treated with FR 139317 (20 mg/kg intraperitoneally, twice daily) it increased only from 196 +/- 4 to 212 +/- 3 mm Hg during a treatment period of 6 weeks. There was also an increase in heart weight. At the end of the experiment the plasma levels of atrial natriuretic peptide and brain natriuretic peptide were significantly lower in the group treated with FR 139317 than in the controls. The endothelin plasma levels were significantly higher and the plasma renin activity was lower in the group treated with the endothelin receptor antagonist. These data indicate that endothelin is involved in the maintenance of high blood pressure and cardiac hypertrophy in malignant hypertension, as exemplified by SHR-SP.

引用

页码：1128 / 1134

页数：7

共 41 条

[31]

Bird, Waldron, Incomplete inhibition of endothelin-1 pressor effects by an endothelin ET<sub>A</sub> receptor antagonist, Eur J Pharmacol, 240, pp. 295-298, (1993)

[32]

Loffler, Brev, Clozel, Effect of different endothelin receptor antagonists and of the novel nonpeptide antagonist Ro 46- 2005 on endothelin levels in rat plasma, FEBS Letters, 333, pp. 108-110, (1993)

[33]

Goldberg, Tanaka, Barchowsky, Effects of losartan on blood pressure, plasma renin activity, and angiotensin II in volunteers, Hypertension, 21, pp. 704-713, (1993)

[34]

Neuser, Stasch, Knorr, Et al., Inhibition by atrial natriuretic peptide of endothelin-1-stimulated proliferation of vascular smooth muscle cells, J Cardiovasc Pharmacol, 22, pp. S257-S261, (1993)

[35]

Battistini, Chailler, D'Orleans-Juste, Et al., Growth regulatory properties of endothelins, Peptides, 14, pp. 385-399, (1993)

[36]

Miller, Burnett, Circulating paracrine and autocrine mechanisms in heart failure, Curr Opinion Cardiol, 8, pp. 376-382, (1993)

[37]

Nakao, Itoh, Suga, Et al., The natriuretic peptide family, Curr Opinion Nephrol Hypertens, 2, pp. 45-50, (1993)

[38]

Stasch, Hirth-Dietrich, Kazda, Et al., Endothelin stimulates release of atrial natriuretic peptides in vitro and in vivo, Life Sci, 45, pp. 869-875, (1989)

[39]

Gellai, Jugus, Fletcher, Et al., Reversal of postischaemic acute renal failure with a selective ET<sub>A</sub> receptor antagonist in the rat, Kidney Int, 93, pp. 900-906, (1994)

[40]

Davies, Haleen, Doherty, Et al., Effects of selective endothelin antagonists on the hemodynamic response to cyclosporin A, J Am Soc Nephrol, 4, pp. 1448-1454, (1994)

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