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Central role of heterocellular gap junctional communication in endothelium‐dependent relaxations of rabbit arteries
Author(s) -
Chaytor A. T.,
Evans W. H.,
Griffith T. M.
Publication year - 1998
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1998.561bq.x
Subject(s) - endothelium , aorta , gap junction , biophysics , phenylephrine , acetylcholine , cyclopiazonic acid , chemistry , anatomy , vasodilation , extracellular , medicine , endocrinology , biochemistry , biology , intracellular , blood pressure
1 The contribution of gap junctions to endothelium‐dependent relaxation was investigated in isolated rabbit conduit artery preparations pre‐constricted by 10 μM phenylephrine (PhE). 2 Acetylcholine (ACh) relaxed the thoracic aorta by ≈60 % and the superior mesenteric artery (SMA) by ≈90 %. A peptide possessing sequence homology with extracellular loop 2 of connexin 43 (Gap 27, 300 μM) inhibited relaxation by ≈40 % in both artery types. Gap 27 also attenuated the endothelium‐dependent component of the relaxation induced by ATP in thoracic aorta but did not modify force development in response to PhE. 3 NG ‐nitro‐L‐arginine methyl ester (L‐NAME, 300 μM), an inhibitor of NO synthase, attenuated ACh‐induced relaxation by ≈90 % in the aorta but only by ≈40 % in SMA ( P < 0.05 ). Residual L‐NAME‐insensitive relaxations were almost abolished by 300 μM Gap 27 in aorta and inhibited in a concentration‐dependent fashion in SMA (≈50 % at 100 μM and ≈80 % at 10 mM). Gap 27 similarly attenuated the endothelium‐dependent component of L‐NAME‐insensitive relaxations to ATP in aorta. 4 Responses to cyclopiazonic acid, which stimulates endothelium‐dependent relaxation through a receptor‐independent mechanism, were also attenuated by Gap 27, whereas this peptide exerted no effect on the NO‐mediated relaxation induced by sodium nitroprusside in preparations denuded of endothelium. 5 ACh‐induced relaxation of ‘sandwich’ mounts of aorta or SMA were unaffected by Gap 27 but completely abolished by L‐NAME. 6 We conclude that direct heterocellular communication between the endothelium and smooth muscle contributes to endothelium‐dependent relaxations evoked by both receptor‐dependent and ‐independent mechanisms. The inhibitory effects of Gap 27 peptide do not involve homocellular communication within the vessel wall or modulation of NO release or action.