© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Effects of endothelin receptor antagonists and nitric oxide on myogenic tone and 
-adrenergic-dependent contractions of rabbit resistance arteries
Institut de Cardiologie de Montréal, Centre de Recherche, 5000, Rue Bélanger Est, Montréal, Que., Canada H1T 1C8
* Corresponding author. Tel.: +1-514-376-3330, ext: 3589; fax: +1-514-376-1355 thorin{at}icm.umontreal.ca
Regulation of vascular contractions by endothelium-derived endothelin-1 (ET-1) and nitric oxide (NO) may vary depending on the stimulus. Objectives: To investigate if ET-1 receptor stimulation and NO contributed to a similar extent to the regulation of pressure- and 
-adrenergic receptor (AR) agonist-induced smooth muscle contraction. Methods: Rabbit mesenteric arteries (150–200 µm) were isolated, cannulated and pressurized. Changes in diameter were recorded as a function of the perfusion pressure (PP) or -AR agonist addition at a PP of 60 mmHg. All experiments were performed in the presence of indomethacin (10 µmoll–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
-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 
30%. Phenylephrine (Phe), an 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 2-AR agonist, induced contraction; the sensitivity to OXY (pD=2, 7.7±0.2) was unaffected by L-NOARG, bosentan or BQ 123. Conclusion: Our results indicate that pressure-induced tone is independently regulated by endothelium-derived NO and ET-1. In contrast, 1-AR stimulation-induced tone is sensitive to ET-1 in the absence of NO, whereas occupation of 2-AR mediates a contraction unregulated by the endothelium.
KEYWORDS AR, adrenergic receptor; EDHF, endothelium-derived hyperpolarizing factor; ET-1, endothelin-1; L-NOARG, N-nitro-L-arginine; MT, myogenic tone; NO, nitric oxide; OXY oxymetazoline; Phe, phenylephrine; PP, perfusion pressure; PSS, physiological salt solution
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