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The effects of nifedipine on α 2 ‐adrenoceptor‐mediated contractions in several isolated blood vessels from the rabbit
Author(s) -
Dunn W.R.,
Daly C.J.,
McGrath J.C.,
Wilson V.G.
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb09816.x
Subject(s) - nifedipine , dihydropyridine , vein , blood vessel , medicine , calcium channel , endocrinology , artery , calcium , chemistry
1 The effects of the dihydropyridine calcium channel blocker, nifedipine, on noradrenaline‐induced contractile responses have been examined in several isolated blood vessels from the rabbit, with particular emphasis on responses mediated via postjunctional α 2 ‐adrenoceptors. 2 In the isolated renal vein, ear vein, distal saphenous artery, saphenous vein and plantaris vein, 0.1 μ m and 1 μ m nifedipine reduced responses elicited by 54 m m KCl by more than 70%. The remaining responses were abolished by α‐adrenoceptor blockade, suggesting the involvement of noradrenaline released from neurones activating a dihydropyridine‐resistant mechanism. 3 In the renal vein (α 1 ), ear vein (predominantly α 2 ‐), distal saphenous artery (α r ‐ > α 2 ‐), saphenous vein and plantaris vein (α 2 ‐ > α 1 ‐), 0.01 μ m and 0.1 μ m nifedipine produced concentration‐related reductions in the maximum response to noradrenaline. However, 1 μ m nifedipine was no more effective than 0.1 μ m nifedipine and the reduction in the maximum varied from 10–25% of the control response. Thus, a sizeable component of the α‐adrenoceptor‐medaited response in all blood vessels is resistant to dihydropyridine calcium channel blockers and this appears to be unrelated to the α‐adrenoceptor subtype involved. 4 Following irreversible inactivation of α 1 ‐adrenoceptors and isolation of functional α 2 ‐adrenoceptors in the saphenous vein, plantaris vein and distal saphenous artery (the latter requiring the presence of angiotensin II), the effect of nifedipine on responses to noradrenaline was increased. However, a component of the α 2 ‐adrenoceptor response in each preparation was present even after the concentration of nifedipine was increased to 1 μ m . 5 In the saphenous vein, a preparation in which it has been demonstrated previously that α 2 ‐adrenoceptor‐mediated responses are highly dependent upon the presence of extracellular calcium ions, partial depolarization with 20 m m KCl failed to increase the inhibitory effect of 0.1 μ m nifedipine. This suggests the involvement of dihydropyridine‐resistant Ca 2+ channels. The possible relationship between these dihydropyridine‐resistant Ca 2+ channels, α‐adrenoceptor subtypes and ‘receptor‐operated’ Ca 2+ channels is discussed.