Endothelium-derived relaxing factor and nitroprusside compared in noradrenaline- and K+-contracted rabbit and rat...

1. The effects of endothelium-derived relaxing factor (EDRF) (as stimulated by acetylcholine in the presence of endothelium), sodium nitroprusside and 8-bromocyclic GMP on mechanical relaxation, calcium (45Ca) influx and cyclic GMP levels were studied in isolated rabbit aortic preparations pre-contracted either by noradrenaline or by high (120 mM) extracellular potassium. 2. The results confirmed a relatively greater effect of these three interventions on mechanical relaxation and on reducing calcium influx in noradrenaline-contracted than in potassium-contracted preparations. 3. The increase in cyclic GMP levels induced by sodium nitroprusside, contrary to previous reports, was no greater in noradrenaline-stimulated preparations than in potassium-stimulated preparations, a finding confirmed in rat aortic preparations, and relaxation was not associated with a significant reduction of calcium influx in the potassium-stimulated preparations. 4. Cyclic GMP-mediated relaxation of potassium contraction thus appears to be due to actions of cyclic GMP other than on calcium influx. 5. These findings suggest that cyclic GMP reduces calcium influx more through receptor-operated channels than through voltage-operated channels. 6. The endothelium-dependent acetylcholine-induced elevation of cyclic GMP was reduced both by noradrenaline and by high extracellular potassium, possibly by altering release or activity of EDRF. 7. The sensitivity of the soluble guanylate cyclase system to stimulation by EDRF and nitrovasodilators appears to be greater in rat than rabbit aortic preparations.