Endothelium-derived relaxing factor inhibits the formation of inositol trisphosphate by rabbit aorta.

1. The effects of endothelium-derived relaxing factor (EDRF), sodium nitroprusside, 8-bromo-cyclic GMP and atrial natriuretic factor (ANF) on inositol trisphosphate (IP3) levels were studied in isolated rabbit aortic preparations stimulated with noradrenaline. 2. In endothelium-containing preparations, acetylcholine, which stimulated EDRF release, inhibited noradrenaline-stimulated IP3 formation. The EDRF inhibitor haemoglobin reversed this effect. 3. In endothelium-denuded preparations, sodium nitroprusside, 8-bromo-cyclic GMP and ANF each similarly inhibited the rise in IP3 levels stimulated by noradrenaline. 4. These findings show that in rabbit aorta, agents which increase cyclic GMP inhibit the noradrenaline-induced rise in IP3 levels and may provide an explanation for the previously reported observations that cyclic GMP inhibits the noradrenaline-stimulated increase in calcium influx and release of intracellular calcium in vascular smooth muscle.