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 positive inotropic responses of guinea-pig left atria and papillary muscles and positive chronotropic responses of right atria to sympathomimetic amines were examined at 38 degrees and 30 degrees C. At the lower temperature, supersensitivity to orciprenaline and isoprenaline was exhibited as shifts of the dose-response curves to the left and significant reductions in EC50 values. This supersensitivity could not be attributed to reduced metabolism since the experiments were performed in the presence of metanephrine (10(-5)M) and U-0521 (3',4'-dihydroxy-2-methylpropiophenone) (10(-4)M) as inhibitors of extraneuronal uptake and catechol-O-methyltransferase (COMT) respectively, and the agonists are not susceptible to neuronal uptake. After incubation of the tissues with Ro 03-7894 (1-(5-chloracetylaminobenzfuran-2-yl)-2-isopropylaminoethanol), followed by its prolonged washout (greater than 2h), the maximum responses to isoprenaline and orciprenaline were depressed, confirming the apparently irreversible beta-adrenoceptor antagonism. Dissociation constants (KA) for isoprenaline and orciprenaline were determined from the equiactive concentrations obtained before (A) and after (A') incubation with Ro 03-7894, plotted as 1/A against 1/A' (KA = (slope-1)/intercept). KA values were the same for orciprenaline in the three cardiac preparations and for isoprenaline in the atria. This applied at 38 degrees and 30 degrees C and indicates that the beta-adrenoceptors mediating the inotropic and chronotropic responses of the guinea-pig heart do not differ. The KA values of both agonists were, however, consistently and significantly lower at 30 degrees than at 38 degrees C, indicating an increase in affinity. 8 It is concluded that hypothermia-induced supersensitivity of cardiac tissue to sympathomimetic amines is associated with an increase in their affinity for the B-adrenoceptors.
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PMID:Temperature-induced changes in dissociation constants (KA) of agonists at cardiac beta-adrenoceptors determined by use of the irreversible antagonist Ro 03-7894. 614 43

The present study sought to quantitate the levels of plasma catecholamines [norepinephrine (NE), epinephrine (E), and dopamine (DA)] during induction and rewarming from hypothermia. Male rats (317 +/- 8 g) were made hypothermic by exposure to 0.9% halothane at -10 to -15 degrees C while blood pressure (carotid artery), heart rate, and colonic temperature (Tc) were monitored. Anesthesia was discontinued when Tc reached 28 degrees C. Tc continued to fall but was held at 20-20.5 degrees C for 30 min. Rewarming was then initiated by raising ambient temperature to 22 degrees C. Arterial blood samples were taken 1) before cooling, 2) just before rewarming, 3) when Tc reached 22 degrees C during rewarming, and 4) when Tc reached 27 degrees C during rewarming. Plasma was assayed radioenzymatically for catecholamines using both phenylethanolamine-N-methyltransferase and catechol-O-methyltransferase procedures, and hypothermic induction resulted in significant increases in NE, E, and DA above control levels (P less than 0.01). With rewarming to Tc = 22 degrees C, all catecholamines increased above the level observed during hypothermia (P less than 0.01), and NE and DA increased still further (P less than 0.01) when Tc reached 27 degrees C. The levels of plasma catecholamines observed during hypothermia and during the rewarming phase indicate a role of the sympathoadrenal medullary system in the metabolic adjustments associated with hypothermia and recovery. During rewarming, the levels of E and NE attained exceed those at which both substances may be expected to act as circulating hormones.
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PMID:Plasma catecholamines in rats during rewarming from induced hypothermia. 649 Apr 67