title: Effects of endothelin receptor antagonists and nitric oxide on myogenic tone and alpha-adrenergic-dependent contractions of rabbit resistance arteries.
abstract: Regulation of vascular contractions by endothelium-derived endothelin-1 (ET-1) and nitric oxide (NO) may vary depending on the stimulus.
  
  
  OBJECTIVE
  To investigate if ET-1 receptor stimulation and NO contributed to a similar extent to the regulation of pressure- and alpha-adrenergic receptor (AR) agonist-induced smooth muscle contraction.
  
  
  METHODS
  Rabbit mesenteric arteries (150-200 microns) were isolated, cannulated and pressurized. Changes in diameter were recorded as a function of the perfusion pressure (PP) or alpha-AR agonist addition at a PP of 60 mmHg. All experiments were performed in the presence of indomethacin (10 mumol 1(-1)).
  
  
  RESULTS
  At a PP of 60 mmHg, myogenic tone (MT) developed to represent 17 +/- 1% of the minimal diameter. The magnitude of the MT was increased by 140% (P < 0.05) by the inhibition of NO production with N omega-nitro-L-arginine (L-NOARG). Bosentan, an ETA/B receptor antagonist, and BQ 123, a selective ETA receptor antagonist, decreased (P < 0.05) MT either alone or in combination with L-NOARG by approximately 30%. Phenylephrine (Phe), an alpha 1-AR agonist, induced contraction; the sensitivity to Phe (pD2, 6.2 +/- 0.2) was unaffected by bosentan or BQ 123 alone but increased (P < 0.05) by L-NOARG (pD2, 7.3 +/- 0.5). Further addition of bosentan or BQ 123 restored the sensitivity to Phe to its control value. Oxymetazoline (OXY), an alpha 2-AR agonist, induced contraction; the sensitivity to OXY (pD = 2, 7.7 +/- 0.2) was unaffected by L-NOARG, bosentan or BQ 123.
  
  
  CONCLUSIONS
  Our results indicate that pressure-induced tone is independently regulated by endothelium-derived NO and ET-1. In contrast, alpha 1-AR stimulation-induced tone is sensitive to ET-1 in the absence of NO, whereas occupation of alpha 2-AR mediates a contraction unregulated by the endothelium.
authors.affiliation: Institut de Cardiologie de Montréal, Centre de Recherche, Montréal, Que., Canada.
authors.forename: T D
authors.initials: TD
authors.lastname: Nguyen
authors.forename: P
authors.initials: P
authors.lastname: Véquaud
authors.forename: E
authors.initials: E
authors.lastname: Thorin
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D000077300:Bosentan; D065128:Endothelin Receptor Antagonists; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology*; D010109:Oxymetazoline / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D013449:Sulfonamides / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D065128:Endothelin Receptor Antagonists; D004791:Enzyme Inhibitors; D010456:Peptides, Cyclic; D013449:Sulfonamides; D010656:Phenylephrine; D019335:Nitroarginine; D010109:Oxymetazoline; D019001:Nitric Oxide Synthase; D000077300:Bosentan; C072247:cyclo(Trp-Asp-Pro-Val-Leu)