title: The role of myoendothelial cell contact in non-nitric oxide-, non-prostanoid-mediated endothelium-dependent relaxation of porcine coronary artery.
abstract: 1. Experiments were designed to analyse the requirement of myoendothelial junctions by bradykinin-induced endothelium-dependent relaxations resistant to NG-nitro-L-arginine (L-NOARG) and indomethacin porcine coronary arteries. 2. Rings of porcine coronary arteries were contracted with the thromboxane receptor agonist, U46619 and relaxations to bradykinin recorded isometrically. All experiments were performed in the presence of indomethacin. Nitric oxide (NO)-mediated effects were blocked by the NO synthase inhibitor L-NOARG (250 microM) and myoendothelial contacts inhibited by treatment with hypertonic solution containing D-mannitol or sucrose (each 180 mM) or the gap junctional uncoupling agent 1-heptanol (2 mM). High [K+] solutions (40 mM) were used to probe a possible contribution of endothelium-derived hyperpolarizing factor (EDHF). 3. In the presence of endothelium, bradykinin induced concentration-dependent relaxations with a mean EC50 of 3.2 nM and a maximum response of 95 +/- 1% of papaverine-induced relaxation (control curve). 4. In the absence of endothelium, bradykinin failed to induce relaxations. Addition of cultured porcine aortic endothelial cells to the organ bath resulted in some relaxation and restored in part the relaxant effect of bradykinin. This endothelial cell-mediated relaxant effect was completely abolished in the presence of 250 microM L-NOARG. 5. Bradykinin-induced relaxations in endothelium-preserved rings were only slightly suppressed by L-NOARG (86% of control). In vessels partially depolarized by high extracellular [K+] (40 mM) relaxation was reduced to 72% of control. In the presence of L-NOARG, bradykinin failed to relax partially depolarized vessels. 6. In the presence of 2 mM -heptanol, 180 mM mannitol or 180 mM sucrose maximum relaxation to bradykinin was reduced to ~70%, i.e. to the same extent as in the presence of high [K+]. The remaining relaxation was sensitive to blockade by L-NOARG.7. Tissue cyclic GMP content which reflects NO activity, was increased about 4 fold by bradykinin(300 nM). This increase was unaffected by high [K+], heptanol or sucrose but blocked by L-NOARG.8 Our results suggest that non-nitric oxide- and non-prostanoid-mediated endothelium-dependent relaxation of porcine coronary artery requires functionally intact myoendothelial junctions.
authors.affiliation: Institu Für Pharmakologie and Toxikologie, Universitãt Graz, Austria.
authors.forename: E
authors.initials: E
authors.lastname: Kühberger
authors.forename: K
authors.initials: K
authors.lastname: Groschner
authors.forename: W R
authors.initials: WR
authors.lastname: Kukovetz
authors.forename: F
authors.initials: F
authors.lastname: Brunner
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001685:Biological Factors / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000502:physiology*; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology; D019335:Nitroarginine; D010208:Papaverine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D013552:Swine; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D001685:Biological Factors; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; C067410:endothelium-dependent hyperpolarization factor; D019335:Nitroarginine; D009569:Nitric Oxide; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001120:Arginine; D010208:Papaverine; D006152:Cyclic GMP; D011188:Potassium; D001920:Bradykinin