Beta-adrenoceptor agonist mediated relaxation of rat isolated resistance arteries: a role for the endothelium and nitric oxide.
1. Isoprenaline (10(-9)-10(-5) M) relaxed rat isolated mesenteric resistance arteries pre-contracted with K+ (30-60 mM) (p EC50 (M) 8.03 +/- 0.40; maximum relaxation 66.79 +/- 2.43%, n = 7). This relaxation was partially attenuated by the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 10(-4) M). 2. The beta 2-adrenoceptor agonist, salbutamol (10(-9)-10(-5) M), produced a modest maximum relaxation (35.93 +/- 2.93%), which was not sensitive to L-NAME. 3. The beta 1-adrenoceptor agonist, dobutamine (10(-9)-10(-5) M), relaxed arteries precontracted with K+. This relaxation was abolished by L-NAME (10(-4) M) and also by propranolol (10(-6) M), but not affected by D-NAME (10(-4) M). The inhibition by L-NAME was partially reversed by L-arginine (10(-3) M). Removal of the endothelium severely attenuated relaxation to dobutamine. 4. Contractile responses to depolarizing K+ solutions were enhanced by the addition of L-NAME, and also by removal of the endothelium. 5. The above findings demonstrate that beta 1-adrenoceptor causes relaxation via NO release from the endothelium of rat mesenteric resistance arteries. In addition, contraction to K+ is modified by release of NO from the endothelium, possibly in response to tension development.
Graves
J
J
Division of Physiology, United Medical School, London.
Poston
L
L
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D004280:Dobutamine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D014655:Vascular Resistance / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D005576:Colforsin; D009569:Nitric Oxide; D004280:Dobutamine; D001120:Arginine; D011433:Propranolol; D000242:Cyclic AMP; D007545:Isoproterenol; D000420:Albuterol; D011188:Potassium; D019331:NG-Nitroarginine Methyl Ester