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Systemic vascular resistance ([R.sub.sys]) of freshwater turtles increases substantially during anoxia, but the underlying mechanisms are not fully understood. We investigated whether hydrogen sulfide ([H.sub.2]S), an endogenously produced metabolite believed to be an [O.sub.2] sensor/ transducer of vasomotor tone, contributes to the increased [R.sub.sys] of anoxic red-eared slider turtles (Trachemys scripta). Vascular infusion of the [H.sub.2]S donor Naris in anesthetized turtles at 21[degrees]C and fully recovered normoxic turtles at 5[degrees]C and 21[degrees]C revealed [H.sub.2]S to be a potent vasoconstrictor of the systemic circulation. Likewise, wire myography of isolated turtle mesenteric and pulmonary arteries demonstrated [H.sub.2]S to mediate an anoxia-induced constriction. Intriguingly, however, Naris did not exert vasoconstrictory effects during anoxia (6 h at 21[degrees]C; 14 days at 5[degrees]C) when plasma [H.sub.2]S concentration, estimated from the colorimetric measurement of plasma acid-labile sulfide concentration, likely increased by ~3-and 4-fold during anoxia at 21[degrees]C, and 5[degrees]C, respectively. Yet, blockade of endogenous [H.sub.2]S production by DL-propargylglycine or hydroxylamine (0.44 mmol/kg) partially reversed the decreased systemic conductance ([G.sub.sys]) exhibited by 5[degrees]C anoxic turtles. These findings suggest that the signal transduction pathway of [H.sub.2]S-mediated vasoactivity is either maximally activated in the systemic circulation of anoxic turtles and/or that it is oxygen dependent. red-eared slider; anoxia; temperature; cardiovascular; systemic resistance; pulmonary resistance; blood pressure; heart doi: 10.1152/ajpregu.00521.2009.

The intrinsic heart rate of most vertebrates studied, including humans, is elevated during digestion, suggesting that a nonadrenergic-noncholinergic factor contributes to the postprandial tachycardia. The regulating factor, however, remains elusive and difficult to identify. Pythons can ingest very large meals, and digestion is associated with a marked rise in metabolism that is sustained for several days. The metabolic rise causes more than a doubling of heart rate and a fourfold rise in cardiac output. This makes the python an interesting model to investigate the postprandial tachycardia. We measured blood pressure and heart rate in fasting Python regius, and at 24 and 48 h after ingestion of a meal amounting to 25% of body wt. Digestion caused heart rate to increase from 25 to 56 min, whereas blood pressure was unchanged. The postprandial rise in heart rate was partially due to a doubling of intrinsic heart rate. The [H.sub.2]-antagonist did not affect heart rate of fasting snakes but decreased heart rate by 15-20 min at 24 h into digestion, whereas it had no effects at 48 h. Thus, the histaminergic tone on the heart rose from none to 30% at 24 h but vanished after 48 h. In anesthetized snakes, histamine caused a systemic vasodilatation and a marked increase in heart rate and cardiac output mediated through a direct effect on [H.sub.2]receptors. Our study strongly indicates that histamine regulates heart rate during the initial phase of digestion in pythons. This study describes a novel regulation of the vertebrate heart. reptile; digestion; heart rate; blood flow; blood pressure

[O.sub.2] chemoreceptors elicit cardiorespiratory reflexes in all vertebrates, but consensus on [O.sub.2]-sensing signal transduction mechanism(s) is lacking. We recently proposed that hydrogen sulfide ([H.sub.2]S) metabolism is involved in [O.sub.2] sensing in vascular smooth muscle. Here, we examined the possibility that [H.sub.2]S is an [O.sub.2] sensor in trout chemoreceptors where the first pair of gills is a primary site of aquatic [O.sub.2] sensing and the homolog of the mammalian carotid body. Intrabuccal injection of [H.sub.2]S in unanesthetized trout produced a dose-dependent bradycardia and increased ventilatory frequency and amplitude similar to the hypoxic response. Removal of the first, but not second, pair of gills significantly inhibited [H.sub.2]S-mediated bradycardia, consistent with the loss of aquatic chemoreceptors, mRNA for [H.sub.2]S-synthesizing enzymes, cystathionine [beta]-synthase and cystathionine [gamma]-lyase, was present in branchial tissue. Homogenized gills produced [H.sub.2]S enzymatically, and [H.sub.2]S production was inhibited by [O.sub.2], whereas mitochondrial [H.sub.2]S consumption was [O.sub.2] dependent. Ambient hypoxia did not affect plasma [H.sub.2]S in unanesthetized trout, but produced a [Po.sub.2]-dependent increase in a sulfide moiety suggestive of increased [H.sub.2]S production. In isolated zebrafish neuroepithelial cells, the putative chemoreceptive cells of fish, both hypoxia and [H.sub.2]S, produced a similar ~10-mV depolarization. These studies are consistent with [H.sub.2]S involvement in [O.sub.2] sensing/signal transduction pathway(s) in chemoreceptive cells, as previously demonstrated in vascular smooth muscle. This novel mechanism, whereby [H.sub.2]S concentration ([[H.sub.2]S]) is governed by the balance between constitutive production and oxidation, tightly couples tissue [[H.sub.2]S] to [Po.sub.2] and may provide an exquisitely sensitive, yet simple, [O.sub.2] sensor in a variety of tissues. hydrogen sulfide concentration

Hydrogen sulfide ([H.sub.2]S) is rapidly emerging as a biologically significant signaling molecule. Studies published before 2000 report low or undetectable [H.sub.2]S (usually as total sulfide) levels in blood or plasma, whereas recent work has reported sulfide concentrations between 10 and 300 [micro]M, suggesting it acts as a circulating signal. In the first series of experiments, we used a recently developed polarographic sensor to measure the baseline level of endogenous [H.sub.2]S gas and turnover of exogenous [H.sub.2]S gas in real time in blood from numerous animals, including lamprey, trout, mouse, rat, pig, and cow. We found that, contrary to recent reports, [H.sub.2]S gas was essentially undetectable (< 100 nM total sulfide) in all animals. Furthermore, exogenous sulfide was rapidly removed from blood, plasma, or 5% bovine serum albumin in vitro and from intact trout in vivo. To determine if blood [H.sub.2]S could transiently increase, we measured oxygen-dependent [H.sub.2]S production by trout hearts in vitro and in vivo. [H.sub.2]S has been shown to mediate ischemic preconditioning (IPC) in mammals. [PC is present in trout and, unlike mammals, the trout myocardium obtains its oxygen from relatively hypoxic systemic venous blood. In vitro, myocardial [H.sub.2]S production was inversely related to P[O.sub.2], whereas we failed to detect [H.sub.2]S in ventral aortic blood from either normoxic or hypoxic fish in vivo. These results provide an autocrine or paracrine mechanism for myocardial coupling of hypoxia to [H.sub.2]S in [PC, i.e., oxygen sensing, but they fail to provide any evidence that [H.sub.2]S signaling is mediated by the circulation. gasotransmitter; hydrogen sulfide metabolism; vascular signaling

Digestion of large meals in pythons produces substantial increases in heart rate and cardiac output, as well as a dilation of the mesenteric vascular bed leading to intestinal hyperemia, but the mediators of these effects are unknown. Bolus intra-arterial injections of python neurotensin ([[His.sup.3], [Val.sup.4], [Ala.sup.7]]NT) (1 - 1,000 pmol/kg) into the anesthetized ball python Python regius (n = 7) produced a dose-dependent vasodilation that was associated with a decrease in systemic pressure ([P.sub.sys]) and increase in systemic blood flow ([Q.sub.sys]). There was no effect on pulmonary pressure and conductance. A significant (P < 0.05) increase in heart rate ([f.sub.H]) and total cardiac output ([Q.sub.tot]) was seen only at high doses (>30 pmol/kg). The systemic vasodilation and increase in [Q.sub.tot] persisted after [beta]-adrenergic blockade with propranolol, but the rise in [f.sub.H] was abolished. Also, the systemic vasodilation persisted after histamine [H.sub.2]-receptor blockade. In unanesthetized pythons (n = 4), bolus injection of python NT in a dose as low as 1 pmol/kg produced a significant increase in blood flow to the mesenteric artery (177% [+ or -] 54%; mean [+ or -] SE) and mesenteric conductance (219% [+ or -] 74%) without any increase in [Q.sub.sys], systemic conductance, [P.sub.sys], and [f.sub.H]. The data provide evidence that NT is an important hormonal mediator of postprandial intestinal hyperemia in the python, but its involvement in mediating the cardiac responses to digestion may be relatively minor. blood flow; mesenteric artery; heart rate

Low [O.sub.2] levels in the lungs of birds and mammals cause constriction of the pulmonary vasculature that elevates resistance to pulmonary blood flow and increases pulmonary blood pressure. This hypoxic pulmonary vasoconstriction (HPV) diverts pulmonary blood flow from poorly ventilated and hypoxic areas of the lung to more well-ventilated parts and is considered important for the local matching of ventilation to blood perfusion. In the present study, the effects of acute hypoxia on pulmonary and systemic blood flows and pressures were measured in four species of anesthetized reptiles with diverse lung structures and heart morphologies: varanid lizards (Varanus exanthematicus), caimans (Caiman latirostris), rattlesnakes (Crotalus durissus), and tegu lizards (Tupinambis merianae). As previously shown in turtles, hypoxia causes a reversible constriction of the pulmonary vasculature in varanids and caimans, decreasing pulmonary vascular conductance by 37 and 31%, respectively. These three species possess complex multicameral lungs, and it is likely that HPV would aid to secure ventilation-perfusion homogeneity. There was no HPV in rattlesnakes, which have structurally simple lungs where local ventilation-perfusion inhomogeneities are less likely to occur. However, tegu lizards, which also have simple unicameral lungs, did exhibit HPV, decreasing pulmonary vascular conductance by 32%, albeit at a lower threshold than varanids and caimans (6.2 kPa oxygen in inspired air vs. 8.2 and 13.9 kPa, respectively). Although these observations suggest that HPV is more pronounced in species with complex lungs and functionally divided hearts, it is also clear that other components are involved. hypoxia; pulmonary circulation; systemic circulation

Incubation of heat-denatured plasma from the rattlesnake Crotalus atrox with trypsin generated a bradykinin (BK) that contained two amino acid substitutions ([Arg.sup.1] [right arrow] Val and [Ser.sup.6] [right arrow] Thr) compared with mammalian BK. Bolus intra-arterial injections of synthetic rattlesnake BK (0.01-10 nmol/kg) into the anesthetized rattlesnake, Crotalus durissus terrificus, produced a pronounced and concentration-dependent increase in systemic vascular conductance (Gsys). This caused a fall in systemic arterial blood pressure (Psys) and an increase in blood flow. Heart rate and stroke volume also increased. This primary response was followed by a significant rise in Psys and pronounced tachycardia (secondary response). Pretreatment with [N.sup.G]-nitro-L-arginine methyl ester reduced the NK-induced systemic vasodilatation, indicating that the effect is mediated through increased NO synthesis. The tachycardia associated with the late primary and secondary response to BK was abolished with propranolol and the systemic vasodilatation produced in the primary phase was also significantly attenuated by pretreatment, indicating that the responses are caused, at least in part, by release of cathecholamines and subsequent stimulation of [beta]-adrenergic receptors. In contrast, the pulmonary circulation was relatively unresponsive to BK. reptile; vasoactive kinin; catecholamines; nitric oxide; adrenergic receptor