alpha-Adrenoceptor mechanisms of thermoregulation during cold challenge in humans

1. Previous studies on the thermoregulatory effects of alpha-adrenoceptor antagonists have been performed primarily in animals and the findings have been inconsistent. There is evidence for thermoregulatory impairment by alpha-adrenergic antagonists in humans not exposed to cold, but the effects of alpha-adrenergic blockade during cold challenge have not been investigated. 2. Fourteen healthy human volunteers (seven elderly, aged 55-68 years and seven young, aged 19-27 years) were studied on three separate days and received three randomly assigned treatments; (i) control (no drug), (ii) low-dose phentolamine and (iii) high-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, peripheral vasoconstriction and metabolic heat production were measured. 3. The alpha-adrenoceptor antagonist caused a dose-dependent inhibition of vasoconstriction in the elderly but did not impair vasoconstriction 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 selective inhibition of vasoconstriction (but not shivering) by alpha-adrenoceptor antagonism in elderly individuals. Compared with the young, the elderly are more sensitive to the effects of alpha-antagonists, perhaps due to downregulation of the alpha-adrenoceptor. These findings lead us to conclude that thermoregulatory vasoconstriction is alpha-adrenergically mediated, and this response is attenuated by alpha-adrenoceptor blockade in elderly humans.