The role of NO-cGMP pathway and potassium channels on the relaxation induced by clonidine in the rat mesenteric arterial bed.

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.

Endothelium-dependent vasodilator effect of Euterpe oleracea Mart. (Açaí) extracts in mesenteric vascular bed of the rat.

Açai (Euterpe oleracea Mart.) a fruit from the Amazon region, largely consumed in Brazil is rich in polyphenols. Experiments were undertaken to determine whether hydro-alcoholic extract obtained from stone of açaí induces a vasodilator effect in the rat mesenteric vascular bed precontracted with norepinephrine (NE) and, if so, to elucidate the underlying mechanism. Açai stone extract (ASE, 0.3-100 microg) induced a long-lasting endothelium-dependent vasodilation that was significantly reduced by N(G)-nitro-l-arginine methyl ester (l-NAME) and (1)H-[1,2,3] oxadiazolo [4,4-a] quinoxalin-l-one (ODQ) and abolished by KCl (45 mM) plus l-NAME. In vessels precontrated with NE and KCl (45 mM) or treated with K(Ca)(+2) channel blockers (charybdotoxin plus apamin), the effect of ASE was significantly reduced. However this effect is not affect by indomethacin, glybenclamide and 4-aminopiridine. Atropine, pyrilamine, yohimbine and HOE 140 significantly reduced the vasodilator effect of acetylcholine, histamine, clonidine and bradykinin, respectively, but did not change the vasodilator effect of ASE. In cultured endothelial cells ASE (100 microg/mL) induced the formation of NO that was reduced by N(G)-nitro-l-arginine (l-NA, 100 microM). The present study demonstrates that the vasodilator effect of ASE is dependent on activation of NO-cGMP pathway and may also involve endothelium-derived hyperpolarizing factor (EDHF) release. The vasodilator effect suggest a possibility to use ASE as a medicinal plant, in the treatment of cardiovascular diseases.

Antihypertensive, vasodilator and antioxidant effects of a vinifera grape skin extract.

Cumulative evidence suggests that moderate wine consumption exerts a cardioprotective effect. We investigated the occurrence of an antihypertensive effect of an alcohol-free hydroalcoholic grape skin extract (GSE) obtained from skins of a vinifera grape (Vitis labrusca) in experimental rodent hypertension models. The vasodilator effect of GSE (polyphenols concentration 55.5 mg g(-1)) was also assessed in the isolated mesenteric vascular bed of Wistar rats and the antioxidant effect was studied on lipid peroxidation of hepatic microsomes. Oral administration of GSE significantly reduced systolic, mean and diastolic arterial pressure in Wistar rats with desoxycorticosterone acetate-salt and N(G)-nitro-L-arginine methyl ester (L-NAME) induced experimental hypertension. In the rat isolated mesenteric vascular bed pre-contracted with norepinephrine, bolus injections of GSE induced endothelium-dependent vasodilatation that was substantially inhibited by L-NAME, but not by indometacin, tetraethylammonium or glibenclamide. Lipid peroxidation of hepatic microsomes estimated as malondialdehyde production was concentration-dependently inhibited by GSE. In conclusion, the antihypertensive effect of GSE might be owing to a combination of vasodilator and antioxidant actions of GSE. These findings also suggest that the beneficial effect of moderate red wine consumption could be owing to an antihypertensive action induced by compounds occurring in the skin of vinifera grapes.

Bronchodilator activity of Mikania glomerata Sprengel on human bronchi and guinea-pig trachea.

The effects of aqueous extracts and hydro-alcoholic extract (HAE), and of a dichloromethane fraction (MG1) obtained from the HAE of Mikania glomerata leaves on isolated respiratory and vascular smooth muscle have been investigated. Aqueousextracts and HAE induced a significant inhibition on the histamine contractions on the isolated guinea-pig trachea. HAE extract induced a concentration-dependent relaxation on guinea-pig trachea pre-contracted with histamine (IC50 0.34 (0.29-0.39) mg mL(-1)), acetylcholine (IC50 0.72 (0.67-0.77) mg mL(-1)) or K+ (IC50 1.41 (1.18-1.64) mg mL(-1)) and on isolated human bronchi precontracted with K+ (IC50 0.34 (0.26-0.42) mg mL(-1)). The dichloromethane fraction induced a concentration dependent relaxation in guinea-pig trachea precontracted with K+ (IC50 0.017 (0.012-0.022) mg mL(-1)). The dichloromethane fraction had also a small vasodilator effect on the isolated mesenteric vascular bed and on the isolated rat aorta, and a significant reduction of the oedema induced by subplantar injections of Bothropsjararaca venom in mice. When tested on plasmid DNA, MG1 did not damage the DNA. Chromatographic analysis showed the presence of 11.4% w/w coumarin in MG1. The results supported the indication of M. glomerata products for the treatment of respiratory diseases where bronchoconstriction is present.