Nature of hypo- and hyperthermia induced by the calcium antagonist nicardipine.
The effects of nicardipine, a calcium channel blocking agent, injected into the cerebral ventricles, (i.c.v.), on the body temperature of unanaesthetized cats have been investigated. Nicardipine produced a biphasic effect on body temperature: a transient dose-dependent decline followed by a longlasting elevation. The fall, but not the rise, of body temperature was associated with a dose-dependent increase in respiration. Yohimbine, in small doses, but not prazosin and propranolol, when injected into the cerebral ventricles, attenuated the hypothermia evoked by i.c.v. nicardipine. However, all the antagonists, except yohimbine in large doses, depressed the hyperventilation induced by nicardipine. Calcium chloride (i.c.v.) reversed, while i.c.v. methysergide virtually had no effect on hyperthermia caused by i.c.v. nicardipine. Nicardipine virtually had no effect on body temperature of intracerebroventricular reserpine- and alpha-methyl-p-tyrosine-treated cats. It appears, therefore, that nicardipine at least in part evoked hypothermia through alpha-2 adrenoceptors located presynaptically, while nicardipine-induced respiratory changes are mediated also partly via alpha-adrenoceptors having mixed alpha 1 and alpha 2 properties. The hyperthermic effect of nicardipine, on the contrary, is mainly due to an action on voltage-dependent calcium ion channels. The contribution of the hyperventilation to the hypothermic effect of nicardipine cannot be of great importance, since the hypothermia was accompanied with hypoventilation when alpha- and beta-adrenoceptor blocking agents were used.
D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D002415:Cats; D005334:Fever / Q000139:chemically induced; D007035:Hypothermia / Q000139:chemically induced; D007276:Injections, Intraventricular; D007473:Ion Channels / Q000187:drug effects; D009529:Nicardipine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D012119:Respiration / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D007473:Ion Channels; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D011433:Propranolol; D009529:Nicardipine; D011224:Prazosin