C. Cariotoumaniantz et al., ANTAGONISM OF ALPHA(1)-ADRENOCEPTOR AGONIST-INDUCED RESPONSES BY RILMENIDINE IN VASCULAR SMOOTH-MUSCLE, European journal of pharmacology, 341(2-3), 1998, pp. 179-185
The effect of the centrally acting antihypertensive agent, rilmenidine
, was examined on the contractile properties of isolated rat portal ve
in strips and on the free cytosolic [Ca2+] ([Ca2+](i)) in isolated myo
cytes. Rilmenidine (1-30 mu M) relaxed strips precontracted with norad
renaline. This effect was not inhibited by the alpha(2)-adrenoceptor a
ntagonist, yohimbine, and was not mimicked by the alpha(2)-adrenocepto
r agonist, -N-(45-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK 14,3
04). Rilmenidine dose dependently shifted to the right the concentrati
on-response curves to noradrenaline and to phenylephrine but not that
to carbachol. Rilmenidine alone (0.1-30 mu M) caused a contraction whi
ch maximally corresponded to 18% of the maximal noradrenaline-induced
contraction. This effect was not produced by UK 14,304, was not affect
ed by yohimbine, but was inhibited by the alpha(1)-adrenoceptor antago
nist, prazosin. In isolated myocytes, rilmenidine reduced the noradren
aline-induced [Ca2+](i) increase but alone, it produced a rise in [Ca2
+](i), the peak amplitude of which averaged 15% of the noradrenaline-i
nduced transient [Ca2+](i) rise. It is concluded that rilmenidine acts
as a partial agonist of alpha(1)-adrenoceptors of vascular smooth mus
cle, causing relaxation of vessels precontracted by full agonists of a
lpha(1)-adrenoceptors. (C) 1998 Elsevier Science B.V.