The role of NO-cGMP pathway and potassium channels on the relaxation induced by clonidine in the rat mesenteric arterial bed.
Vascul Pharmacol
; 46(5): 353-9, 2007 May.
Article
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| MEDLINE
| ID: mdl-17258511
ABSTRACT
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 alpha(2) adrenoceptor inhibitors yohimbine (1-3 microM) and rauwolscine (1 microM). 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 microM) but was not affected by indomethacin (3-10 microM) 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 microM). The Ca(2+)-dependent K+ channel (K+(Ca2+)) inhibitors, charybdotoxin (ChTx; 0.1 microM) plus apamin (0.1 microM), 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, glibenclamide (10 microM), 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 (K(V)) blocker, 4-aminopyridine (4-AP, 1 mM). In conclusion, our results demonstrate that clonidine activates alpha(2)-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.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Vasodilatación
/
Vasodilatadores
/
Canales de Potasio
/
Clonidina
/
GMP Cíclico
/
Agonistas alfa-Adrenérgicos
/
Arterias Mesentéricas
/
Óxido Nítrico
Límite:
Animals
Idioma:
En
Revista:
Vascul Pharmacol
Asunto de la revista:
ANGIOLOGIA
/
FARMACOLOGIA
Año:
2007
Tipo del documento:
Article
País de afiliación:
Brasil