Effects of endothelin receptor antagonists and nitric oxide on myogenic tone and alpha-adrenergic-dependent contractions of rabbit resistance arteries

• Published in: Cardiovascular research 1999-08, Vol.43 (3), p.755-761
• Main Authors: Nguyen, T D, Véquaud, P, Thorin, E
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-2 Receptor Antagonists; Adrenergic alpha-Agonists - pharmacology; Animals; Bosentan; Endothelin Receptor Antagonists; Enzyme Inhibitors - pharmacology; In Vitro Techniques; Male; Mesenteric Arteries; Nitric Oxide Synthase - antagonists & inhibitors; Nitroarginine - pharmacology; Oxymetazoline - pharmacology; Peptides, Cyclic - pharmacology; Phenylephrine - pharmacology; Rabbits; Sulfonamides - pharmacology; Vasoconstriction - drug effects
• ISSN: 0008-6363
• DOI: 10.1016/S0008-6363(99)00170-4

Regulation of vascular contractions by endothelium-derived endothelin-1 (ET-1) and nitric oxide (NO) may vary depending on the stimulus. 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. 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)). 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. 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.