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SUMMARYThe roles of nitric oxide synthase activity (NOS), nitrite and myoglobin (Mb) in the regulation of myocardial function during hypoxia were examined in trout and goldfish, a hypoxia-intolerant and hypoxia-tolerant species, respectively. We measured the effect of NOS inhibition, adrenaline and nitrite on the O 2 consumption rate and isometric twitch force development in electrically paced ventricular preparations during hypoxia, and measured O 2 affinity and nitrite reductase activity of the purified heart Mbs of both species. Upon hypoxia (9% O 2 ), O 2 consumption and developed force decreased in both trout and goldfish myocardium, with trout showing a significant increase in the O 2 utilization efficiency, i.e. the ratio of twitch force to O 2 consumption, suggesting an increased anaerobic metabolism. NOS inhibition enhanced myocardial O 2 consumption and decreased efficiency, indicating that mitochondrial respiration is under a tone of NOS-produced NO. When trout myocardial twitch force and O 2 consumption are enhanced by adrenaline, this NO tone disappears. Consistent with its conversion to NO, nitrite reduced O 2 consumption and increased myocardial efficiency in trout but not in goldfish. Such a difference correlates with the lower O 2 affinity measured for trout Mb that would increase the fraction of deoxygenated heme available to catalyze the reduction of nitrite to NO. Whereas lowaffinity trout Mb would favor O 2 diffusion within cardiomyocytes at high in vivo O 2 tensions, goldfish Mb having higher O 2 affinity and higher nitrite reductase activity appears better suited to facilitate O 2 diffusion and nitrite reduction in the heart during severe hypoxia, a condition particularly well tolerated by this species.

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(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(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.

Painted turtles (Chrysemys picta) survive months of anoxic submergence, which is associated with large changes in the extracellular milieu where pH falls by 1, while extracellular K+, Ca++, and adrenaline levels all increase massively. While the effect of each of these changes in the extracellular environment on the heart has been previously characterized in isolation, little is known about their interactions and combined effects. Here we examine the isolated and combined effects of hyperkalemia, acidosis, hypercalcemia, high adrenergic stimulation, and anoxia on twitch force during isometric contractions in isolated ventricular strip preparations from turtles. Experiments were performed on turtles that had been previously acclimated to warm (25 degrees C), cold (5 degrees C), or cold anoxia (submerged in anoxic water at 5 degrees C). The differences between acclimation groups suggest that cold acclimation, but not anoxic acclimation per se, results in a downregulation of processes in the excitation-contraction coupling. Hyperkalemia (10 mmol L(-1) K+) exerted a strong negative inotropic effect and caused irregular contractions; the effect was most pronounced at low temperature (57%-97% reductions in twitch force). Anoxia reduced twitch force at both temperatures (14%-38%), while acidosis reduced force only at 5 degrees C (15%-50%). Adrenergic stimulation (10 micromol L(-1)) increased twitch force by 5%-19%, but increasing extracellular [Ca++] from 2 to 6 mmol L(-1) had only small effects. When all treatments were combined with anoxia, twitch force was higher at 5 degrees C than at 25 degrees C, whereas in normoxia twitch force was higher at 25 degrees C. We propose that hyperkalemia may account for a large part of the depressed cardiac contractility during long-term anoxic submergence.

2+from the SR for force development in a frequency and tissue dependent manner. This is discussed in the context of the development of high reptilian heart rates and blood pressures.