期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 281, 期 2, 页码 H606-H612出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.2001.281.2.H606
关键词
fura 2; endothelial calcium fluorescence ratio; calcium-independent pathways; tyrosine kinase; endothelium-derived hyperpolarizing factor
资金
- NHLBI NIH HHS [HL-46813, P0-1HL-43023] Funding Source: Medline
In cultured endothelial cells, Ca2+-dependent and -independent activation of nitric oxide (NO) synthesis to agonists and flow/wall shear stress (WSS) has been demonstrated. However, the presence and function of these pathways are less well known in microvessels that can be exposed to a high level of WSS. We hypothesized that the role of changes in endothelial intracellular calcium concentration ([Ca2+](i)) is different in agonist- and WSS-induced release of NO. Thus changes in endothelial [Ca2+](i) and diameter of intact pressurized (similar to 100 mum at 80 mmHg) gracilis skeletal muscle arterioles of rats were measured by fluorescent video-microscopy. Acetylcholine (ACh) and increases in WSS (by increasing intraluminal flow) elicited dilations (maximum 91 +/- 2% and 34 +/- 4%) that could be inhibited by N-omega-nitro-L-arginine methyl ester (L-NAME), a NO synthase blocker. In diameter-clamped arterioles, ACh caused substantial increases in the endothelial calcium fluorescence ratio (ERCa, maximum 43 +/- 5%), which was significantly greater than changes in ERCa (maximum similar to 10%) to increases in WSS. The Ca2+ ionophore A-23187 also substantially increased ERCa (maximum 38 +/- 5%) and elicited significant L-NAME-sensitive arteriolar dilations (maximum 45 +/- 7%). Intraluminal administration of the tyrosine kinase inhibitor genistein had no effect on dilations induced by ACh or the NO donor sodium nitroprusside, whereas it eliminated WSS-induced dilations. Collectively, our data suggest that, in endothelium of skeletal muscle arterioles, NO synthesis is activated by shear stress without a substantial increase in [Ca2+](i), most likely by activation of tyrosine kinase pathways, whereas NO release by ACh and A-23187 is associated with substantial increases in [Ca2+](i).
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