Myoendothelial coupling in the mesenteric arterial bed; segmental differences and interplay between nitric oxide and endothelin-1.
OBJECTIVE
We tested the hypothesis that activated arterial smooth muscle (ASM) stimulates endothelial vasomotor influences via gap junctions and that the significance of this myoendothelial coupling increases with decreasing arterial diameter.


METHODS
From WKY rats, first-, second-, third- and fourth-order branches of the superior mesenteric artery (MA1, MA2, MA3 and MA4 respectively) were isolated and mounted in wire-myographs to record vasomotor responses to 0.16-20 micromol x L(-1) phenylephrine.


RESULTS
Removal of endothelium increased the sensitivity (pEC(50)) to phenylephrine in all arteries. The nitric oxide (NO) synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) (100 micromol x L(-1)) did not modify pEC(50) to phenylephrine in all denuded arteries, and increased it in intact MA1, MA2 and MA3 to the same extent as denudation. However, in intact MA4, the effect of L-NAME was significantly larger (DeltapEC(50) 0.57 +/- 0.02) than the effect of endothelium removal (DeltapEC(50) 0.20 +/- 0.06). This endothelium-dependent effect of L-NAME in MA4 was inhibited by (i) steroidal and peptidergic uncouplers of gap junctions; (ii) a low concentration of the NO donor sodium nitroprusside; and (iii) by the endothelin-receptor antagonist bosentan. It was also observed during contractions induced by (i) calcium channel activation (BayK 8644, 0.001-1 micromol x L(-1)); (ii) depolarization (10-40 mmol x L(-1) K(+)); and (iii) sympathetic nerve stimulation (0.25-32 Hz).


CONCLUSIONS
These pharmacological observations indicated feedback control by endothelium of ASM reactivity involving gap junctions and a balance between endothelium-derived NO and endothelin-1. This myoendothelial coupling was most prominent in distal resistance arteries.
Hilgers
R H P
RH
Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands.
De Mey
J G R
JG
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D000077300:Bosentan; D002120:Calcium Channel Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism*; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D066298:In Vitro Techniques; D008638:Mesenteric Arteries / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D009213:Myography; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D019899:Paracrine Communication / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D017466:Receptors, Endothelin / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D002120:Calcium Channel Agonists; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D020030:Nitric Oxide Donors; D017466:Receptors, Endothelin; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D019001:Nitric Oxide Synthase; D000077300:Bosentan; D019331:NG-Nitroarginine Methyl Ester