Circulation Research. 2002;90:1108-1113
Published online before print April 25, 2002, doi: 10.1161/01.RES.0000019756.88731.83
Published online before print April 25, 2002, doi: 10.1161/01.RES.0000019756.88731.83
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© 2002 American Heart Association, Inc.
Cellular Biology |
Involvement of Myoendothelial Gap Junctions in the Actions of Endothelium-Derived Hyperpolarizing Factor
From the Department of Physiology (M.T., H.A.C., H.C.P.), Monash University, Clayton, Victoria, Australia; Division of Neuroscience (S.L.S., C.E.H.), John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia.
Correspondence to Marianne Tare, Department of Physiology, PO Box 13F, Monash University, Victoria 3800, Australia. E-mail marianne.tare{at}med.monash.edu.au
The nature of the vasodilator endothelium-derived hyperpolarizing factor (EDHF) is controversial, putatively involving diffusible factors and/or electrotonic spread of hyperpolarization generated in the endothelium via myoendothelial gap junctions (MEGJs). In this study, we investigated the relationship between the existence of MEGJs, endothelial cell (EC) hyperpolarization, and EDHF-attributed smooth muscle cell (SMC) hyperpolarization in two different arteries: the rat mesenteric artery, where EDHF-mediated vasodilation is prominent, and the femoral artery, where there is no EDHF-dependent relaxation. In the rat mesenteric artery, stimulation of the endothelium with acetylcholine (ACh) evoked hyperpolarization of both ECs and SMCs, and characteristic pentalaminar MEGJs were found connecting the two cell layers. In contrast, in the femoral artery, ACh evoked hyperpolarization in only ECs but not in SMCs, and no MEGJs were present. Selective hyperpolarization of ECs or SMCs evoked hyperpolarization in the other cell type in the mesenteric artery but not in the femoral artery. Disruption of gap junctional coupling using the peptide Gap 27 markedly reduced the ACh-induced hyperpolarization in SMCs, but not in ECs, of the mesenteric artery. These results show that transfer of EC hyperpolarization or of a small molecule to SMCs through MEGJs is essential and sufficient to explain EDHF.
Key Words: endothelium-derived hyperpolarizing factor • myoendothelial gap junctions • endothelium • smooth muscle • electrical coupling
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