α-Adrenoceptor mechanisms of thermoregulation during cold challenge in humans

1. Previous studies on the thermoregulatory effects of α-adrenoceptor antagonists have been performed primarily in animals and the findings have been inconsistent. There is evidence for thermoregulatory impairment by α-adrenergic antagonists in humans not exposed to cold, but the effects of α-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°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 α-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 α-adrenergic blockade in the elderly or in the young. 4. These findings illustrate the selective inhibition of vasoconstriction (but not shivering) by α-adrenoceptor antagonism in elderly individuals. Compared with the young, the elderly are more sensitive to the effects of α-antagonists, perhaps due to downregulation of the α-adrenoceptor. These Endings lead us to conclude that thermoregulatory vasoconstriction is α-adrenergically mediated, and this response is attenuated by α-adrenoceptor blockade in elderly humans.