Characterisation of smooth muscle α-Adrenoceptors and of responses to electrical stimulation in the cat isolated perfused middle cerebral artery

Summary

The effects of periarterial electrical stimulation and of drugs with α-adrenoceptor agonist or antagonist activity were examined in cat isolated perfused middle cerebral arteries, in order to characterise the smooth muscle adrenoceptors. The perfused vessel preparation was stable and did not develop intrinsic tone when perfused at 5 ml/min with Krebs' solution. Exogenous noradrenaline caused increases in perfusion pressure, the pD₂ value being 6.8±0.1. The maximum effect of noradrenaline was only 22±4% of that of KCl (127 mM). Adrenaline was equipotent with noradrenaline whereas dopamine and phenylephrine were approximately 100 times less potent. The α₂-adrenoceptor antagonist RX 781094 (0.1–10 μM) caused concentration-dependent rightward shifts in the noradrenaline concentration-response curve (in the presence of 4μM cocaine and 1 μM propranolol), although the antagonism was not of a simple competitive nature. Prazosin (0.3 μM) failed to produce a significant shift to the right in the concentration effect curve to noradrenaline; however, the effects of maximal concentrations of noradrenaline were slightly but significantly reduced. If tone was induced in the vessels, tetrodotoxinsensitive dilatations could be produced by electrical stimulation. In the absence of tone, the same stimulation parameters were ineffective in causing vasoconstriction. Increasing pulse width or voltage led to substantial vasoconstrictor responses, which were resistant to tetrodotoxin. These results demonstrate that in a cerebral artery which does not show a sympathetic vasoconstrictor response to electrical stimulation, both α₁- and α₂-adrenoceptors appear to be present on smooth muscle cells although the responses to exogenous noradrenaline are predominantly mediated by the α₂-adrenoceptor subtype.