Factors affecting angiotensin II-induced hypothermia in rats

Abstract

Systemic administration of angiotensin II (AII) to the rat has previously been shown to induce a dose-dependent, hypothermic response manifested by a fall in colonic temperature (CT), a decrease in heat production and an increase in tail skin temperature (TST). The factors mediating AII-induced hypothermia and their site of action were the subjects of the present investigation. To this end, intracerebroventricular administration of 1 μg of AII induced a 0.4°C reduction in CT and a 2.4°C increase in TST. In contrast, SC administration of 200 μg angiotensin III/kg induced a slight increase in CT but had no affect on TST. Pretreatment with the AII-receptor antagonist, saralasin, at either 1 or 10 μg/kg, SC did not affect either the fall in CT or the increase in TST induced by administration of 200 μg AII/kg, SC. However, the administration of 100 μg saralasin/kg, SC attenuated both the fall in CT and the increase in TST induced by either 100 or 200 μg AII/kg. Since both the presynaptic alpha adrenoceptor agonist, clonidine, and the opioid antagonist, naloxone, modulate the pressor and dipsogenic responses to AII, their effects on AII-induced hypothermia were tested. Both clonidine (25 μg/kg, SC) and naloxone (1 mg/kg, IP) enhanced the fall in CT. Clonidine lengthened the duration of the increase in TST while naloxone had no effect. Pretreatment with the presynaptic adrenoceptor antagonist, yohimbine (300 μg/kg, SC), did not alter the hypothermic response to administration of AII. To determine whether vasodilation of the tail of the rat was mediated by AII-induced prostaglandin release, indomethacin (4 and 6 mg/kg) was administered. The increase in TST accompanying administration of AII was not affected by pretreatment with indomethacin, while the fall in CT was actually augmented. Thus, the mechanisms by which AII induces hypothermia appear to be specific, yet different from those mediating the dipsogenic and pressor responses to AII.