期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 282, 期 5, 页码 H1724-H1731出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00699.2001
关键词
vascular smooth muscle; calcium sensitivity; cytochrome P-450
资金
- NHLBI NIH HHS [HL-59996, HL-29587, R37 HL036279, HL-10407] Funding Source: Medline
This study examined the mechanism by which cGMP contributes to the vasodilator response to nitric oxide (NO) in rat middle cerebral arteries (MCA). Administration of a NO donor, diethylaminodiazen-1- ium-1,2-dioate (DEA-NONOate), or 8-bromo-cGMP (8-BrcGMP) increased the diameter of serotonin-preconstricted MCA by 79 +/- 3%. The response to DEA-NONOate, but not 8-BrcGMP, was attenuated by iberiotoxin (10(-7) M) or a 80 mM high-K+ media, suggesting that activation of K+ channels contributes to the vasodilator response to NO but not 8-BrcGMP. The effects of NO and cGMP on the vasoconstrictor response to Ca2+ were also studied in MCA that were permeabilized with alpha-toxin and ionomycin. Elevations in bath Ca2+ from 10(-8) to 10(-5) M decreased the diameter of permeabilized MCA by 76 +/- 5%. DEA-NONOate (10(-6) M) and 8-BrcGMP (10(-4) M) blunted this response by 60%. Inhibition of guanylyl cyclase with 1H-[1,2,4] oxadiazole[4,3-a] quinoxalin-1-one (10(-5) M) blocked the inhibitory effect of the NO donor, but not 8-BrcGMP, on Ca2+-induced vasoconstriction. 8-BrcGMP (10(-4) M) had no effect on intracellular Ca2+ concentration ([Ca2+](i)) in control, serotonin-stimulated, or alpha-toxin- and ionomycin-permeabilized vascular smooth muscle cells isolated from the MCA. These results indicate that the vasodilator response to NO in rat MCA is mediated by activation of Ca2+-activated K+ channels via a cGMP-independent pathway and that cGMP also contributes to the vasodilator response to NO by decreasing the contractile response to elevations in [Ca2+](i).
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