Participação dos fatores derivados do endotélio no efeito vasodilatador da clonidina

Abstract

The mechanisms involved in the vasodilation action of clonidine have not been completely elucidated yet. We investigated the potential mechanisms that seem to be involved using rat isolated mesenteric arterial bed (MAB). In precontracted MAB, clonidine (10-300 pmol) induced a dose-dependent relaxation, that was inhibited by endothelium removal (deoxycholic acid) and was significantly reduced by the α2-adrenoceptor inhibitors, yohimbine (1-3 μM) and rauwolscine (1 μM). The endothelium-dependent vasodilation induced by clonidine was reduced by the nitric oxide (NO) synthase inhibitor L-NAME (0.3 mM) and guanylyl cyclase inhibitor ODQ (10 μM) but was not affected by indomethacin (3 -10 μM). In the presence of L-NAME the vasodilator effect of clonidine was further attenuated by high K<SUP>+</SUP> solution (45 mM). The Ca<SUP>2+</SUP>-dependent K<SUP>+</SUP> channel (K<SUB>Ca</SUB>) inhibitors, charybdotoxin (ChTx; 0.1 μM) plus apamin (0.1 μM), also reduced the vasodilation induced by clonidine, however this response was not further reduced in the presence of L-NAME as observed with acetylcholine (10 pmol). In the presence of ATP -dependent K<SUP>+</SUP> channels (K<SUP>+</SUP><SUB>ATP</SUB>) blocker, glybenclamide (10 μM), the inhibitory effect of ChTx plus apamin plus L-NAME was increased. In contrast, the vasodilation induced by clonidine was not affected by voltage-dependent K<SUP>+</SUP> channels (K<SUB>V</SUB>) blocker, 4-aminopiridine (1mM). In conclusion, our results demonstrate that clonidine activates α2-adrenoceptors in rat MAB and that the endothelium-dependent vasodilation is mediated by activation of NO-cGMP pathway and also involves the activation of K<SUB>ATP</SUB> and K<SUB>Ca</SUB> channels. An endothelium-derived hyperpolarizing factor (EDHF) may also participate in the vasodilator response of clonidine.