The effects of 6-nitrodopamine on the systemic vasculature of South American rattlesnakes

Catecholamines may react with other molecules to produce catecholamine derivatives. For example, nitric oxide may induce nitration of dopamine to form 6-nitrodopamine (6-ND). The endogenous production of such a novel catecholamine has been demonstrated in the mammalian and reptilian cardiovascular system, and in vitro studies demonstrate that 6-ND relaxes pre-contracted aortic rings, and acts as a potent chronotropic agent. So far, however, the in vivo effects of 6-ND remain to be characterised in whole organisms. Using South American rattlesnakes (Crotalus durissus), we measured the endogenous production of 6-ND and other catecholamine derivatives in different tissues of the cardiovascular system and the intercostal muscle. We also used myography to measure the vascular reactivity of the mesenteric artery to 6-ND, and we utilised anaesthetised individuals to measure haemodynamic responses to bolus injections of 6-ND (1 μmol kg-1). Except for blood plasma, 6-ND was detected in all tissues studied, and the addition of l-NAME, a blocker of nitric oxide synthesis, did not alter the production of 6-ND, indicating there are alternative biosynthetic pathways. The isolated mesenteric artery contracted in the presence of adrenaline, dopamine, noradrenaline and 6-ND. We also observed a potentiation of the noradrenergic stimulation in the presence of 6-ND. Finally, injection of 6-ND elicited a small but significant reduction in the mesenteric conductance. It is likely that 6-ND per se exerts small effects on overall haemodynamics, but synergises with noradrenaline and possibly other catecholamines to enhance cardiovascular regulation.