Abstract
1. Isoprenaline (3 x 10(-8)-10(-5) M), salbutamol (3 x 10(-7)-10(-4) M) and forskolin (3 x 10(-9)-3 x 10(-7) M) relaxed rat isolated thoracic aortic rings contracted with noradrenaline (10(-7) M). Removal of the endothelium from the aortic rings abolished the effect of acetylcholine (10(-6) M) and completely prevented the vascular relaxation induced by isoprenaline, salbutamol or forskolin. 2. The isoprenaline concentration-relaxation curve was shifted in parallel to the right about 10 fold by propranolol (3 x 10(-7) M) with no change in the maximum response, showing that the relaxation was mediated by a beta-adrenoceptor. 3. The inhibitor of nitric oxide synthesis, NG-nitro-L-arginine (L-NOARG; 10(-5) M), shifted the isoprenaline relaxation curve to the right and reduced the maximum response. 4. Isoprenaline (10(-6) M) relaxed noradrenaline-induced tone by approximately 95% and at the same time increased levels of adenosine 3':5'-cyclic monophosphate (cyclic AMP) 4 fold and guanosine 3':5'-cyclic monophosphate (cyclic GMP) 12 fold in the aortic rings. Sodium nitroprusside (3 x 10(-8) M) relaxed noradrenaline-evoked tone by 82% without changing levels of cyclic AMP but raised cyclic GMP 19 fold. 5. Forskolin (10(-7) M) relaxed noradrenaline-induced tone by approximately 41% and, like isoprenaline, increased levels of cyclic AMP (2.5 fold) and cyclic GMP (12 fold) in the aortic rings. 6. Removal of the endothelium abolished the relaxant effects of isoprenaline (10(-6) M) and also the associated accumulation of cyclic AMP and cyclic GMP.(ABSTRACT TRUNCATED AT 250 WORDS)
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