Dopamine-induced vasoconstriction is attenuated by endothelial nitric oxide in isolated rat aorta

Dopamine is used to treat shock, congestive heart failure, and renal failure. High doses of dopamine induce vasoconstriction. Endothelial nitric oxide regulates vascular tone and tissue blood flow. However, the role of endothelial nitric oxide on the dopamine-induced vasoconstriction remains unclear. Thus, the goal of this study was to examine the role of endothelial nitric oxide in dopamine-induced vasoconstriction in isolated rat aortas and to elucidate the underlying mechanism, with a particular focus on nitric oxide. Dopamine-induced vasoconstriction was examined in the endothelium-intact and -denuded aortas. Effects of the nitric oxide synthase inhibitor N^w-ntiro-L-arginine methyl ester (L-NAME), non-specific guanylate cyclase (GC) inhibitor methylene blue, nitric oxide-sensitive GC inhibitor 1H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ), calmodulin inhibitor calmidazolium, SCH-23390, sulpiride, haloperidol, and prazosin on dopamine-induced contraction in endothelium-intact aortas were examined. We evaluated the effect of dopamine on cyclic guanosine monophosphate (cGMP) formation in endothelium-intact aortas. The effects of dopamine, haloperidol, and prazosin on endothelial nitric oxide synthase (eNOS) phosphorylation or on calcium levels were examined in human umbilical vein endothelial cells (HUVECs). Dopamine-induced contractions were lower in the endothelium-intact aortas than in the endothelium-denuded aortas. L-NAME, methylene blue, ODQ, and calmidazolium increased dopamine-induced contractions in endothelium-intact aortas, while haloperidol and prazosin inhibited them. SCH-23390 and sulpiride did not significantly alter these contractions. Dopamine increased cGMP formation. Dopamine also increased eNOS phosphorylation and calcium levels in HUVECs, whereas haloperidol or prazosin inhibited these responses. These findings suggest that dopamine-induced vasoconstriction is attenuated by a pathway involving calmodulin-eNOS-GC-cGMP in endothelium-intact rat aortas, mediated by alpha-1 adrenoceptors.