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 inibitor N(omega)-nitro-L-arginine methyl ester (L-NAME, 10(-4) M). 2 The beta2-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 beta1-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 beta1-adrenoceptor activation 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.