Nitric oxide and the cardiovascular actions of histamine

We had found that histamine (HA)-induced relaxation of cavian pulmonary artery is selectively inhibited by N^ω-methyl-l-arginine (NMA) and thus depends on the synthesis ofl-arginine (ARG)-derived EDRF/nitric oxide (NO). We have now assessed whether ARG-derived NO also mediates the coronary-vasodilating effect of HA in the intact heart. Langendorff guinea pig hearts, vasoconstricted by the thromboxane agonist U46619 (86 nM), responded to HA (bolus intra-aortic injections of 1–30 μg) with dose-dependent increases in coronary flow (20–90%), heart rate and contractility. NMA (92 μM) markedly inhibited the HA-induced increase in coronary flow, but not its positive inotropic and chronotropic effects. A similar inhibition was obtained with the NO scavenging compound, Fe²⁺-myoglobin. ARG (1 mM) reestablished the coronary-dilating effects of HA in the presence of NMA. Thus, ARG-derived NO contributes significantly to HA-induced coronary-vasodilatation. Inasmuch as the ultimate HA effect on the coronaries depends on the balance between constriction and relaxation, mediated by smooth muscle and endothelial H₁-receptors, respectively, as well as relaxation due to smooth muscle H₂-receptors, dysfunction of the NO system is likely to precipitate HA-induced vasospasm.