期刊
HYPERTENSION
卷 35, 期 1, 页码 244-248出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.HYP.35.1.244
关键词
norepinephrine; endothelin; protein kinases; arteries; hormones
资金
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R29HL058489] Funding Source: NIH RePORTER
- NHLBI NIH HHS [HL- 58489] Funding Source: Medline
5-Hydroxytryptamine (5-HT)-induced arterial contraction depends on activation of the tyrosine kinase-dependent extracellular signal-regulated mitogen-activated protein kinase (Erk MAPK) pathway. The importance of 5-HT in the control of peripheral resistance has been questioned because circulating free levels of 5-HT are low (in the nanomolar range). We tested the hypothesis that physiologically relevant concentrations of 5-HT potentiate arterial contraction in response to agonists proved to have importance in blood pressure maintenance (norepinephrine [NE] and endothelin-1 [ET-1]) in a tyrosine kinase- and an Erk MAPK-dependent manner. Strips of endothelium-denuded rat tail artery were used for the measurement of isometric force. The general tyrosine kinase inhibitor genistein (5 mu mol/L) and the inhibitor of MAPK/Erk kinase activation PD098059 (10 mu mol/L) shifted concentration-response curves to 5-HT (1x10(-9) to 3x10(-4) mol/L) rightward but did not shift concentration-response curves to NE or ET-1. In separate experiments, 5-HT (10 nmol/L) potentiated contraction in response to NE (20 nmol/L) by approximate to 200% to 300% and to ET-1 (0.3 and 1 nmol/L) by 640% and 180%, respectively. Genistein and PD098059 significantly (66% to 100%) reduced 5-HT-induced potentiation of both NE (20 nmol/L)- and ET-1 (0.3 and 1 nmol/L)-induced contraction. Thus, these data support the ability of low physiological concentrations of 5-HT to amplify arterial responses to hormones with bona fide effects on blood pressure in the novel manner of depending on a tyrosine kinase/Erk MAPK pathway. Although these findings were generated in large arteries, we speculate that they may be applicable to vascular functioning in the; deoxycorticosterone acetate salt model of hypertension in which all 3 hormones, 5-HT, NE, and ET-1, have been implicated as causal factors.
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