Effects of glyceryl trinitrate on endothelium-dependent and -independent relaxation and cyclic GMP levels in rat aorta and human coronary artery.

The effects of glyceryl trinitrate-induced desensitization on relaxations and/or elevated cyclic GMP levels due to the nitrogen oxide-containing vasodilators (glyceryl trinitrate and sodium nitroprusside), the endothelium-dependent vasodilators (acetylcholine and the Ca2+ ionophore A23187), and the atrial peptides (atriopeptin II) were investigated in the rat thoracic aorta and human coronary artery. Prior exposure of rat thoracic aorta to glyceryl trinitrate decreased relaxations to glyceryl trinitrate, sodium nitroprusside, and acetylcholine, whereas relaxations to atriopeptin II and 8-bromo cyclic GMP remained unaltered. In human coronary artery, glyceryl trinitrate pretreatment inhibited relaxations to glyceryl trinitrate, sodium nitroprusside, and the Ca2+ ionophore A23187. Relaxation to glyceryl trinitrate was inhibited more than that to sodium nitroprusside in both tissues. Acetylcholine-induced relaxation in rat thoracic aorta was slightly inhibited, whereas relaxation to the Ca2+ ionophore A23187 in human coronary artery was markedly depressed. Pretreatment with glyceryl trinitrate decreased the elevated cyclic GMP levels due to glyceryl trinitrate and acetylcholine in rat thoracic aorta and to glyceryl trinitrate and the Ca2+ ionophore A23187 in human coronary artery. Removal of the endothelium abolished the increased cyclic GMP levels and relaxation due to the Ca2+ ionophore A23187 and decreased basal cyclic GMP levels in the human coronary artery. In contrast, atriopeptin II-induced increased cyclic GMP levels were unaltered by glyceryl trinitrate pretreatment in rat thoracic aorta. The present results suggest that: glyceryl trinitrate-induced desensitization inhibits relaxation to the nitrogen oxide-containing vasodilators and endothelium-dependent vasodilators in both the rat thoracic aorta and human coronary artery: the inhibition of relaxation is associated with decreased formation of cyclic GMP;(ABSTRACT TRUNCATED AT 250 WORDS)