کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2574968 | 1129727 | 2007 | 7 صفحه PDF | دانلود رایگان |
The mechanisms involved in the vasodilation action of clonidine have not yet been completely elucidated. We investigated the potential mechanisms that seem to be involved in the clonidine vasodilator effect 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 — 2.5 mM) and 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) alone. High K+ (25 mM) solution reduced the vasodilator effect of clonidine that was further attenuated by L-NAME. In the presence of high K+ plus L-NAME, the residual vasodilator effect of clonidine was further reduced by indomethacin (3 μM). The Ca2+-dependent K+ channel (K+Ca2+) 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+ channel (K+ATP) 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+ channels (KV) blocker, 4-aminopiridine (4-AP, 1 mM). 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, hyperpolarization due to activation of K+Ca and K+ATP channels. Prostaglandins might participate in the vasodilator effect of clonidine when NO and EDHF mechanisms are blunted.
Journal: Vascular Pharmacology - Volume 46, Issue 5, May 2007, Pages 353–359