Central role of heterocellular gap junctional communication in endothelium-dependent relaxations of rabbit arteries

• Published in: The Journal of physiology Vol. 508; no. 2; pp. 561 - 573
• Main Authors: Chaytor, A. T., Evans, W. H., Griffith, T. M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK The Physiological Society 15.04.1998; Blackwell Science Ltd; Blackwell Science Inc
• Subjects: Acetylcholine - pharmacology; Adenosine Triphosphate - pharmacology; Animals; Aorta, Thoracic - drug effects; Aorta, Thoracic - innervation; Aorta, Thoracic - physiology; Cell Communication - drug effects; Cell Communication - physiology; Connexin 43 - pharmacology; Endothelium, Vascular - drug effects; Endothelium, Vascular - innervation; Endothelium, Vascular - physiology; Enzyme Inhibitors - pharmacology; Gap Junctions - drug effects; Gap Junctions - physiology; In Vitro Techniques; Indoles - pharmacology; Male; Mesenteric Artery, Superior - drug effects; Mesenteric Artery, Superior - innervation; Mesenteric Artery, Superior - physiology; Muscle Relaxation - drug effects; Muscle Relaxation - physiology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - innervation; Muscle, Smooth, Vascular - physiology; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide Synthase - antagonists & inhibitors; Original; Phenylephrine - pharmacology; Rabbits; Vasoconstrictor Agents - pharmacology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1111/j.1469-7793.1998.561bq.x

The contribution of gap junctions to endothelium-dependent relaxation was investigated in isolated rabbit conduit artery preparations pre-constricted by 10 μ m phenylephrine (PhE). 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 μ m ) 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. N G -nitro-L-arginine methyl ester (L-NAME, 300 μ m ), 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 μ m Gap 27 in aorta and inhibited in a concentration-dependent fashion in SMA (≈50% at 100 μ m and ≈80% at 10 m m ). Gap 27 similarly attenuated the endothelium-dependent component of L-NAME-insensitive relaxations to ATP in aorta. 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. ACh-induced relaxation of ‘sandwich’ mounts of aorta or SMA were unaffected by Gap 27 but completely abolished by L-NAME. 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.