Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Flinders Sensitive Line of rats (FSL) has been selectively bred to have increased sensitivity to cholinergic drugs. Typically, these rats react with twice as great a hypothermic effect to muscarinic agonists such as oxotremorine, as do similarly bred Flinders Resistant Line rats (FRL). We compared the effects of three chemically different calcium channel inhibitors (diltiazem, nicardipine and verapamil) on the hypothermia induced in FRL and FSL rats by oxotremorine (0.2 mg kg-1 s.c.). Each drug was injected i.p. in a dose of 20 mumol kg-1 30 min before oxotremorine. Methylatropine (2 mg kg-1 s.c.) was administered 15 min before oxotremorine to block the peripheral effects of the agonist. The hypothermic effect of oxotremorine in FSL rats was antagonized by nicardipine and diltiazem. In contrast, verapamil failed to influence the hypothermic response in FSL rats. Verapamil significantly (P less than 0.05) augmented oxotremorine hypothermia in FRL rats. Diltiazem and nicardipine were without effect on oxotremorine-induced hypothermia in FRL rats. There were no significant changes in temperature in separate groups of FRL and FSL rats treated with calcium channel inhibitors alone.
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PMID:Effects of calcium channel inhibitors on the hypothermic response to oxotremorine in normo and hypercholinergic rats. 168 Oct 59

The effect of two Ca2+ channel inhibitors (CCIs) on ethanol-induced hypothermia and hypnosis, on tolerance formation to both effects, and on audiogenic convulsions during ethanol withdrawal was studied in rats. Nifedipine, 2 and 5 mg/kg IP, significantly augmented the hypnotic action of ethanol without affecting hypothermia. Diltiazem failed to influence either effect of the toxin. Rectal temperature did not change in ethanol-naive rats after acute injection of diltiazem or nifedipine. Both drugs dose-dependently suppressed the development of tolerance to the hypothermic effect of ethanol without affecting the tolerance to the hypnotic action. Only nifedipine markedly suppressed the audiogenic seizure response in ethanol withdrawn animals. These data suggest that Ca2+ channels play a role in both acute and chronic effects of ethanol while pointing to certain differences in behavioral effects of various CCIs.
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PMID:Different effect of diltiazem and nifedipine on some central actions of ethanol in the rat. 271 89

The effect of diltiazem on creatine kinase release and tissue adenosine triphosphate content was investigated during calcium paradox in the isolated perfused rat heart. Creatine kinase loss was minimal during the calcium-free phase, but there was a 100-fold increase in creatine kinase release after reperfusion with normal calcium-containing medium. Diltiazem reduced creatine kinase loss by 35 percent when added to calcium-free medium and by approximately 80 percent when added to both calcium-free and reperfusion media. Adenosine triphosphate content was significantly increased from 2.98 mumol in untreated calcium paradox hearts to 5 mumol/g dry weight in diltiazem-treated hearts. With hypothermia the calcium paradox injury was completely inhibited if the temperature of calcium-free perfusion was maintained at 15 degrees C. Diltiazem appears to exert its protective effect through its ability to prevent the cellular separation and alterations in the gap junctions during calcium deprivation of cells and to limit calcium entry into the cells after reperfusion with calcium-containing medium.
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PMID:Prevention of calcium paradox-related myocardial cell injury with diltiazem, a calcium channel blocking agent. 628 3

Diltiazem, a calcium slow channel blocker, greatly potentiated and prolonged the antinociceptive effect of morphine in rats. Hypothermia, the primary thermoregulatory effect of morphine, was also potentiated. Verapamil, another calcium blocker elicited corresponding changes in the analgetic and thermoregulatory effects of morphine. These findings seem to be in concert with the suggestions that opiate effects on thermoregulation and nociception are exerted via modulation of calcium fluxes across neural membranes.
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PMID:Potentiation of thermoregulatory and analgesic effects of morphine by calcium antagonists. 650 60

The effects of diltiazem, a sarcolemmal Ca2+ channel blocker, and ryanodine, an inhibitor of sarcoplasmic reticulum function, were investigated in isolated newborn rabbit hearts (2 to 5 days old) subjected to ischemia and reperfusion. After cardioplegic arrest with St. Thomas' Hospital solution, global ischemia was induced at 37 degrees C (normothermia) for 45 minutes or at 20 degrees C (hypothermia) for 180 minutes. The hearts were then reperfused at 37 degrees C for 30 minutes. Diltiazem or ryanodine, at concentrations that have minimal to moderately negative inotropic effects under nonischemic conditions, was added to the cardioplegic solution. After normothermic ischemia, reperfusion of untreated hearts resulted in recovery of left ventricular developed pressure to 52.9% +/- 2.5% of the preischemic level. In hearts treated with diltiazem, recovery of left ventricular developed pressure was significantly improved (84.2% +/- 2.9% at 3 x 10(-8) mol/L; p < 0.01). Comparable improvement was achieved with ryanodine (90.5% +/- 4.1% at 10(-9) mol/L; p < 0.01). Creatine kinase leakage and structural derangement of mitochondria were also reduced by both agents. With hypothermic ischemia, left ventricular developed pressure recovered in untreated hearts to 72.7% +/- 3.3% of preischemic values. Treatment with diltiazem improved the recovery of left ventricular developed pressure to 96.9% +/- 3.5% at 3 x 10(-8) mol/L and reduced creatine kinase leakage and mitochondrial damage. Ryanodine also improved the recovery of left ventricular developed pressure and attenuated ultrastructural damage. These findings suggest that Ca2+ handling by the sarcoplasmic reticulum, like transsarcolemmal Ca2+ influx, plays an important role in the pathogenesis of myocardial ischemia-reperfusion injury in the neonatal heart despite the morphologic and functional immaturity of the sarcoplasmic reticulum in the neonate.
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PMID:Protective effects of diltiazem and ryanodine against ischemia-reperfusion injury in neonatal rabbit hearts. 832 Oct 5

Rats genetically selected for their different ethanol voluntary consumption, UChA (low consumer) and UChB (high consumer) were used. Naive UChA and UChB rats or submitted to ethanol chronic exposure, received an i.p. dose of ethanol (2.76 g/kg) alone or 30 min after an oral dose of diltiazem (10 mg/kg), a calcium channel blocker. A significant potentiation of the narcosis and hypothermia induced by the dose of ethanol was observed in UChA diltiazem-pretreated rats not previously exposed to ethanol, while no potentiation in narcosis time appears in UChA rats chronically exposed to ethanol that acquire tolerance. In the UChB line of rats, diltiazem did not potentiate ethanol depressant actions in naive or chronic ethanol-exposed rats. Diltiazem did not modify ethanol blood levels. These results indicate that the inhibition of voltage-dependent calcium channels can exaggerate ethanol-induced effects in naive rats but not when tolerance was developed. Results suggest that UChB rats may have some innate tolerance that may be due to genetic difference in calcium channel function.
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PMID:Effect of calcium channel blocker diltiazem on some depressant actions of ethanol in UChA and UChB rats. 901 19