1 To assess the involvement of endothelial alpha (2)-adrenoceptors in the c
lonidine-induced vasodilatation, the mesenteric artery of Sprague Dawley ra
ts was cannulated and perfused with Tyrode solution (2 ml min(-1)). We meas
ured perfusion pressure, nitric oxide (NO) in the perfusate using chemilumi
nescence, and tissue cyclic GMP by RIA.
2 In phenylephrine-precontracted mesenteries, clonidine elicited concentrat
ion-dependent vasodilatations associated to a rise in luminal NO. One hundr
ed nM rauwolscine or 100 um L-omega-nitro-L-arginine antagonized the clonid
ine-induced vasodilatation. Guanabenz, guanfacine, and oxymetazoline mimick
ed the clonidine-induced vasorelaxation.
3 In non-contracted mesenteries, 100 nm clonidine elicited a maximal rise o
f NO (123 +/- 13 pmol); associated to a peak in tissue cyclic GMP. Endothel
ium removal, L-omega-nitro-L-arginine, or rauwo1scine ablated the rise in N
O. One hundred nm aminoclonidine, guanfacine, guanabenz, UK14,304 and oxyme
tazoline mimicked the clonidine-induced surge of NO. Ten muM ODQ obliterate
d the clonidine-induced vasorelaxation and the associated tissue cyclic GMP
accumulation; 10-100 nm sildenafil increased tissue cyclic GMP accumulatio
n without altering the clonidine-induced NO release.
4 alpha (2)-Adrenergic blockers antagonized the clonidine-induced rise in N
O. Consistent with a preferential alpha (2D)-adrenoceptor activation, the K
(B)s for yohimbine, rauwolscine, phentolamine, WB4101, and prazosin were: 6
.8, 24, 19, 165, and 1489 nm, respectively.
5 Rat pretreatment with 100 mg kg(-1) 6-hydroxydopamine reduced 95% tissue
noradrenaline and 60% neuropeptide Y. In these preparations, 100 nm clonidi
ne elicited a rise of 91.9 +/- 15.5 pmol NO. Perfusion with 1 muM guanethid
ine or I MM guanethidine plus 1 muM atropine did not modify the NO surge ev
oked by 100 nm clonidine.
6 Clonidine and congeners activate endothelial alpha (2D)-adrenoceptors cou
pled to the L-arginine pathway, suggesting that the antihypertensive action
of clonidine involves an endothelial vasorelaxation mediated by NO release
, in addition to presynaptic mechanisms.