MODULATION OF BARORECEPTOR ACTIVITY BY NITRIC-OXIDE AND S-NITROSOCYSTEINE

被引:79
作者
MATSUDA, T
BATES, JN
LEWIS, SJ
ABBOUD, FM
CHAPLEAU, MW
机构
[1] UNIV IOWA,COLL MED,DEPT INTERNAL MED,IOWA CITY,IA 52242
[2] UNIV IOWA,CTR CARDIOVASC,IOWA CITY,IA 52242
[3] UNIV IOWA,DEPT PHYSIOL & BIOPHYS,IOWA CITY,IA 52242
[4] UNIV IOWA,DEPT ANESTHESIOL,IOWA CITY,IA
[5] UNIV IOWA,DEPT PHARMACOL,IOWA CITY,IA 52242
[6] DEPT VET AFFAIRS MED CTR,IOWA CITY,IA 52242
关键词
CAROTID SINUS; ENDOTHELIUM-DERIVED RELAXING FACTOR; PRESSORECEPTORS; RABBITS;
D O I
10.1161/01.RES.76.3.426
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The goal of this study was to determine whether nitric oxide (NO) and the NO donor, S-nitrosocysteine (cysNO), modulate the activity of carotid sinus baroreceptors. Baroreceptor activity was recorded from the vascularly isolated carotid sinus in anesthetized rabbits. Baroreceptor activity decreased in a dose-dependent manner after injection of either NO or cysNO as constant pressure was maintained, and activity recovered spontaneously over time, within seconds to minutes. The baroreceptor pressure-activity relation was shifted significantly to the right by cysNO, with a profound suppression of activity at high pressure. Baroreceptor activity at 160 mm Hg averaged 76+/-8%, 60+/-6%, and 36+/-5% of the control maximum during exposure to 10(-4), 2 to 3X10(-4), and 10(-3) mol/L cysNO, respectively. The inhibition of activity by the L and D isomers of cysNO was equivalent and was blocked by reduced hemoglobin, suggesting that the effect was mediated by NO. The suppression of baroreceptor activity by cysNO was not related to vascular relaxation as measured by videomicrometer. Inhibition of soluble guanylate cyclase with methylene blue or 6-anilinoquinoline-5,8-quinone (LY83583, 10(-5) mol/L) did not attenuate and dibutyryl cGMP (10(-3) mol/L) did not mimic the suppression of baroreceptor activity by cysNO, suggesting a cGMP-independent mechanism. Activation of endogenous NO formation with thimerosal (10(-5) to 10(-4) mol/L) reduced maxi mum baroreceptor activity in five of eight experiments to 59+/-7% of the control maximum. The NO synthase inhibitor nitro-L-arginine methyl ester (L-NAME, 10(-4) mol/L) by itself failed to influence baroreceptor activity but prevented thimerosal-induced suppression of activity. Addition of L-arginine (10(-3) mol/L) after L-NAME restored the inhibitory influence of thimerosal. The results indicate that NO and cysNO suppress baroreceptor activity through a mechanism independent of guanylate cyclase activation and vascular relaxation and that endogenous NO released by chemical activation suppresses baroreceptor activity.
引用
收藏
页码:426 / 433
页数:8
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