ALPHA-ADRENOCEPTOR MECHANISMS OF THERMOREGULATION DURING COLD CHALLENGE IN HUMANS

1. Previous studies on the thermoregulatory effects of alpha-adrenocep tor antagonists have been performed primarily in animals and the findi ngs have been inconsistent, There is evidence for thermoregulatory imp airment by alpha-adrenergic antagonists in humans not exposed to cold, but the effects of alpha-adrenergic blockade during cold challenge ha ve not been investigated. 2. Fourteen healthy human volunteers (seven elderly, aged 55-68 years and seven young, aged 19-27 years) were stud ied on three separate days and received three randomly assigned treatm ents: (i) control (no drug), (ii) low-dose phentolamine, and (iii) hig h-dose phentolamine, On each day cold intravenous saline (4 degrees C) was given until both vasoconstriction and shivering were triggered or a maximum fluid volume (40 ml/kg) was delivered, Core temperature, pe ripheral vasoconstriction and metabolic heat production were measured. 3. The alpha-adrenoceptor antagonist caused a dose-dependent inhibiti on of vasoconstriction in the elderly but did not impair vasoconstrict ion in the young subjects at the doses that were given, Shivering and metabolic heat production were unaffected by alpha-adrenergic blockade in the elderly or in the young. 4. These findings illustrate the sele ctive inhibition of vasoconstriction (but not shivering) by alpha-adre noceptor antagonism in elderly individuals. Compared with the young, t he elderly are more sensitive to the effects of ct-antagonists, perhap s due to downregulation of the alpha-adrenoceptor. These findings lead us to conclude that thermoregulatory vasoconstriction is alpha-adrene rgically mediated, and this response is attenuated by alpha-adrenocept or blockade in elderly humans.