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Myoendothelial coupling in the mesenteric arterial bed; segmental differences and interplay between nitric oxide and endothelin‐1
Author(s) -
Hilgers RHP,
De Mey JGR
Publication year - 2009
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2009.00128.x
Subject(s) - phenylephrine , nitric oxide , endothelium , endothelin receptor , endocrinology , medicine , vasomotor , sodium nitroprusside , mesenteric arteries , chemistry , anatomy , artery , receptor , blood pressure
Background and purpose: 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. Experimental approach: 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 µmol·L −1 phenylephrine. Key results: Removal of endothelium increased the sensitivity (pEC 50 ) to phenylephrine in all arteries. The nitric oxide (NO) synthase inhibitor N ω ‐nitro‐L‐arginine methyl ester (L‐NAME) (100 µmol·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 (ΔpEC 50 0.57 ± 0.02) than the effect of endothelium removal (ΔpEC 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 µmol·L −1 ); (ii) depolarization (10–40 mmol·L −1 K + ); and (iii) sympathetic nerve stimulation (0.25–32 Hz). Conclusions and implications: 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.