Premium
DIFFERENTIAL ACTIVATION OF ADRENOCEPTOR SUBTYPES BY NORADRENALINE APPLIED FROM THE INTIMAL OR ADVENTITIAL SURFACES OF RAT ISOLATED TAIL ARTERY
Author(s) -
Rajanayagam M. A. S.,
Rand M. J.
Publication year - 1993
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1993.tb03017.x
Subject(s) - idazoxan , vasoconstriction , propranolol , medicine , endothelium , endocrinology , prazosin , norepinephrine , chemistry , artery , blood vessel , receptor , antagonist , dopamine
SUMMARY1 The vasoconstrictor effects of noradrenaline applied to the intimal and adventitial surfaces of perfused segments of rat tail artery in the presence and absence of endothelium were studied. 2 Noradrenaline was about six times more potent as a vasoconstrictor when applied to the intimal than to the adventitial surface. Cocaine (25 μmol/L) enhanced responses to adventitial noradrenaline to a greater extent than those to intimal noradrenaline. A high concentration of propranolol (1 μmol/L) had a similar effect. 3 The vasoconstriction elicited by adventitial noradrenaline declined from a peak whereas that to intimal noradrenaline remained steady. A low concentration of propranolol (0.1 μmol/L) abolished the decline in the response to adventitial noradrenaline. 4 The α 1 ‐ and α 2 ‐adrenoceptor antagonists prazosin (1 nmol/L) and idazoxan (100 nmol/L) significantly reduced responses to intimal and adventitial noradrenaline in the presence or absence of endothelium. 5 Removal of endothelium enhanced responses to intimal but not adventitial noradrenaline. Idazoxan produced a significantly greater reduction of responses to noradrenaline in the absence than in the presence of endothelium, and was more effective against intimal than adventitial noradrenaline. Similar effects were produced by the nitric oxide synthase inhibitor l‐NAME (30 μmol/L). 6 It was concluded that noradrenaline acts on both α 1 ‐ and α 2 ‐adrenoceptors to produce vasoconstriction: the α 1 ‐adrenoceptors appear to be uniformly distributed, whereas α 2 ‐adrenoceptors are located nearer the intima. Intimal noradrenaline also acts on endothelial α 2 ‐adrenoceptors to release EDRF which counteracts the vasoconstrictor action of noradrenaline. Adventitial noradrenaline also acts on β‐adrenoceptors located near the adventitia to counteract the vasoconstriction produced by activation of α‐adrenoceptors and its action is reduced by neuronal uptake.