Acetylcholine‐induced relaxation in blood vessels from endothelial nitric oxide synthase knockout mice
T Chataigneau, M Félétou, PL Huang… - British journal of …, 1999 - Wiley Online Library
T Chataigneau, M Félétou, PL Huang, MC Fishman, J Duhault, PM Vanhoutte
British journal of pharmacology, 1999•Wiley Online LibraryIsometric tension was recorded in isolated rings of aorta, carotid, coronary and mesenteric
arteries taken from endothelial nitric oxide synthase knockout mice (eNOS (−/−) mice) and
the corresponding wild‐type strain (eNOS (+/+) mice). The membrane potential of smooth
muscle cells was measured in coronary arteries with intracellular microelectrodes. In the
isolated aorta, carotid and coronary arteries from the eNOS (+/+) mice, acetylcholine
induced an endothelium‐dependent relaxation which was inhibited by Nω‐l‐nitro‐arginine …
arteries taken from endothelial nitric oxide synthase knockout mice (eNOS (−/−) mice) and
the corresponding wild‐type strain (eNOS (+/+) mice). The membrane potential of smooth
muscle cells was measured in coronary arteries with intracellular microelectrodes. In the
isolated aorta, carotid and coronary arteries from the eNOS (+/+) mice, acetylcholine
induced an endothelium‐dependent relaxation which was inhibited by Nω‐l‐nitro‐arginine …
- Isometric tension was recorded in isolated rings of aorta, carotid, coronary and mesenteric arteries taken from endothelial nitric oxide synthase knockout mice (eNOS(−/−) mice) and the corresponding wild‐type strain (eNOS(+/+) mice). The membrane potential of smooth muscle cells was measured in coronary arteries with intracellular microelectrodes.
- In the isolated aorta, carotid and coronary arteries from the eNOS(+/+) mice, acetylcholine induced an endothelium‐dependent relaxation which was inhibited by Nω‐L‐nitro‐arginine. In contrast, in the mesenteric arteries, the inhibition of the cholinergic relaxation required the combination of Nω‐L‐nitro‐arginine and indomethacin.
- The isolated aorta, carotid and coronary arteries from the eNOS(−/−) mice did not relax in response to acetylcholine. However, acetylcholine produced an indomethacin‐sensitive relaxation in the mesenteric artery from eNOS(−/−) mice.
- The resting membrane potential of smooth muscle cells from isolated coronary arteries was significantly less negative in the eNOS(−/−) mice (−64.8±1.8 mV, n=20 and −58.4±1.9 mV, n=17, for eNOS(+/+) and eNOS(−/−) mice, respectively). In both strains, acetylcholine, bradykinin and substance P did not induce endothelium‐dependent hyperpolarizations whereas cromakalim consistently produced hyperpolarizations (−7.9±1.1 mV, n=8 and −13.8±2.6 mV, n=4, for eNOS(+/+) and eNOS(−/−) mice, respectively).
- These findings demonstrate that in the blood vessels studied: (1) in the eNOS(+/+) mice, the endothelium‐dependent relaxations to acetylcholine involve either NO or the combination of NO plus a product of cyclo‐oxygenase but not EDHF; (2) in the eNOS(−/−) mice, NO‐dependent responses and EDHF‐like responses were not observed. In the mesenteric arteries acetylcholine releases a cyclo‐oxygenase derivative.
British Journal of Pharmacology (1999) 126, 219–226; doi:10.1038/sj.bjp.0702300
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