MECHANISMS OF ENDOTOXIN-INDUCED DILATATION OF CEREBRAL ARTERIOLES

被引:32
作者
BRIAN, JE
HEISTAD, DD
FARACI, FM
机构
[1] UNIV IOWA, COLL MED, CTR CARDIOVASC, DEPT INTERNAL MED, IOWA CITY, IA 52242 USA
[2] UNIV IOWA, COLL MED, CTR CARDIOVASC, DEPT PHARMACOL, IOWA CITY, IA 52242 USA
[3] UNIV IOWA, COLL MED, CTR AGING, IOWA CITY, IA 52242 USA
[4] VET AFFAIRS MED CTR, IOWA CITY, IA 52242 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 1995年 / 269卷 / 03期
关键词
AMINOGUANIDINE; CALCITONIN GENE-RELATED PEPTIDE; INDUCIBLE NITRIC OXIDE SYNTHASE; NITRIC OXIDE; VASODILATATION;
D O I
10.1152/ajpheart.1995.269.3.H783
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Lipopolysaccharide (LPS; endotoxin) produces dilatation of cerebral arterioles in vivo which may be due, in part, to expression of inducible nitric oxide (NO) synthase. We tested the hypothesis that aminoguanidine, an inhibitor of inducible NO synthase, would reduce endotoxin-induced dilatation of cerebral arterioles. Because mechanisms other than expression of inducible NO synthase may contribute to endotoxin-induced dilatation of cerebral arterioles, we also tested the hypothesis that calcitonin gene-related peptide (CORP) contributes to vascular responses to endotoxin. Cerebral arteriolar diameter was measured using a closed cranial window in anesthetized rabbits under control conditions [77 +/- 3 (SE) mu m] and during topical application of endotoxin (100 mu g/ml). After 4 h, diameter of cerebral arterioles increased by 41 +/- 5%. Coapplication of aminoguanidine (0.3 mM) with endotoxin reduced vasodilatation at all time points (30 min to 4 h). Relative to control values, endotoxin treatment increased guanosine 3',5'-cyclic monophosphate (cGMP) concentration in cerebrospinal fluid (CSF) by similar to 20 fold at 4 h. Aminoguanidine attenuated the endotoxin-induced increase in CSF cGMP concentration. Aminoguanidine (0.3 mM) did not alter acetylcholine-mediated dilatation of cerebral arterioles. Coapplication of CGRP-(8-37) (0.5 mu M), a specific blocker of CORP receptors, with endotoxin significantly reduced vasodilatation in response to endotoxin at 2, 3, and 4 h. Thus 1) aminoguanidine inhibits endotoxin- but not acetylcholine-mediated dilatation of cerebral arterioles, and 2) activation of CORP receptors mediates a portion of endotoxin-induced dilation of cerebral arterioles.
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页码:H783 / H788
页数:6
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