Norepinephrine-induced contractions of the rat aorta in the absence of extracellular calcium--III. Effects of cyclic nucleotides.

The rat aorta responds biphasically to norepinephrine (NE) in calcium-free medium. The dissociable phasic and tonic components of the contraction are mediated through alpha-adrenoreceptor activation and mobilization of intracellular calcium. Dibutyryl-cAMP, papaverine (which inhibits cAMP phosphodiesterase and increases cAMP levels), bromo-cGMP, and sodium nitroprusside (which stimulates guanylate cyclase and increases cGMP levels) inhibited in a concentration-dependent manner the biphasic aortic contractions induced by NE in calcium-free medium. The log IC50 values of each of these smooth muscle relaxants for inhibition of the biphasic response to NE in calcium-free medium were very close to those required for inhibition of the contractions induced by NE or KCl in presence of extracellular calcium. The present findings indicate that the phasic and tonic components of NE-induced aortic contractions in calcium-free medium are subject to similar intracellular regulatory mechanisms by cyclic nucleotides at a step subsequent to alpha-adrenoreceptor occupancy by NE, since dibutyryl-cAMP and bromo-cGMP inhibited the tonic component of NE-induced contraction noncompetitively.