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The cardiovascular system of vertebrates is regulated by a vast number of regulatory factors, including histamine. In pythons, histamine induces a strong tachycardia and dilates the systemic vasculature, which resembles the cardiovascular response to the elevated metabolic rate during digestion. In fact, there is an important role of increased histaminergic tone on the heart during the initial 24 h of digestion in pythons. Whilst the cardiovascular effects of histamine are well studied in pythons, little is known about the effects in other groups of reptiles. The histaminergic effects on the heart vary among species and histamine may exert either pressor and depressor effects by causing either constrictive or dilatory vascular responses. Here, we investigated the cardiovascular effects of histamine in three species of reptiles with very different cardiovascular and pulmonary morphologies. Experiments were performed on both anesthetized and recovered animals. We show a species-dependent effect of histamine on the systemic vasculature with dilation in rattlesnakes and constriction in turtles and caimans but no effect on the pulmonary circulation. The histamine-induced dilation in rattlesnakes was mediated through an activation of H-receptors, whereas the histamine-induced constriction in caimans was mediated through both adrenergic signaling and H-receptors activation. In all three species, histamine-induced tachycardia by direct stimulation of histaminergic receptors as well as an indirect activation of adrenoreceptors. This finding highlights a more complex mechanism underlying the action of histamine than previously recognized in reptiles. [ABSTRACT FROM AUTHOR]

Endogenous hydrogen sulfide (H2S) is involved in the regulation of vascular tone. We hypothesized that the lowering of calcium and opening of potassium (K) channels as well as calcium-independent mechanisms are involved in H2S-induced relaxation in rat mesenteric small arteries. Amperometric recordings revealed that free [H2S] after addition to closed tubes of sodium hydrosulfide (NaHS), Na2S, and GYY4137 [P-(4-methoxyphenyl)-P-4-morpholinyl-phosphinodithioic acid] were, respectively, 14%, 17%, and 1% of added amount. The compounds caused equipotent relaxations in isometric myographs, but based on the measured free [H2S], GYY4137 caused more relaxation in relation to released free H2S than NaHS and Na2S in rat mesenteric small arteries. Simultaneous measurements of [H2S] and tension showed that 15 µM of free H2S caused 61% relaxation in superior mesenteric arteries. Simultaneous measurements of smooth muscle calcium and tension revealed that NaHS lowered calcium and caused relaxation of NE-contracted arteries, while high extracellular potassium reduced NaHS relaxation without corresponding calcium changes. In NE-contracted arteries, NaHS (1 mM) lowered the phosphorylation of myosin light chain, while phosphorylation of myosin phosphatase target subunit 1 remained unchanged. Protein kinase A and G, inhibitors of guanylate cyclase, failed to reduce NaHS relaxation, whereas blockers of voltage-gated KV7 channels inhibited NaHS relaxation, and blockers of mitochondrial complex I and III abolished NaHS relaxation. Our findings suggest that low micromolar concentrations of free H2S open K channels followed by lowering of smooth muscle calcium, and by another mechanism involving mitochondrial complex I and III leads to uncoupling of force, and hence vasodilation., (Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.)