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Abstract: Background: Propofol is an alternative to thiopental for induction of general anaesthesia for cesarean section. It crosses the placenta and induces vasodilatation of isolated vessels and may therefore alter fetal placental vascular resistance. The direct effect of propofol on the fetal placental circulation was studied in vitro. The actions of propofol on vasoconstrictive effects induced by angiotensin II (Ang II), bradykinin (BK), prostaglandin F2α (PGF2α) and potassium chloride (KCl) were evaluated. Methods: Full-term healthy human placentas (n=48) were perfused with modified Tyrode’s solution using a pulsatile pump. Placental perfusion pressure was measured in response to injection of Ang II, BK, KCl and PGF2α before and after perfusion with propofol (1.7×10−5 and 5.6×10−5 M). Results: BK, Ang II, KCl and PGF2α induced a dose-dependent increase in placental perfusion pressure. Propofol induced a concentration-dependent decrease in placental perfusion pressure, but this was not observed with the propofol solvent (Intralipid). Propofol, but not Intralipid, reduced the vasoconstrictor effects of BK, KCl and PGF2α, while the effect of Ang II was not changed. The effect of KCl was abolished in placentas perfused with Ca2+-free solution, while the effect of Ang II was not altered. Conclusions: Propofol induced vasodilatation and inhibited the vasoconstrictive effects of BK and PGF2α, in the human placenta. These findings suggest that propofol may not reduce fetal placental blood flow. Since propofol reduced the vasoconstricting effect of KCl but not that of AngII, we propose that the vasodilatory effect of propofol in the human placenta involves inhibition of Ca2+ channels. [Copyright &y& Elsevier]

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 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. [Copyright &y& Elsevier]

Abstract: 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 μg) induced a long-lasting endothelium-dependent vasodilation that was significantly reduced by NG-nitro-l-arginine methyl ester (l-NAME) and 1H-[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 KCa +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 μg/mL) induced the formation of NO that was reduced by NG-nitro-l-arginine (l-NA, 100 μM). 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. [Copyright &y& Elsevier]

Toxicity of an alcohol-free hydro-alcoholic grape skin extract (GSE) obtained from red grapes Vitis labrusca (Isabel varietal) that present antihypertensive, vasodilator and antioxidant effects was estimated by different bioassays. Using the Salmonella/microsome assay for strains TA97, TA98, TA100 and TA102 no mutagenicity was detected for all tested concentrations (0.1–100 μg/ml), even with metabolization. Nevertheless, cytotoxicity was observed for TA97 and TA102 with and without metabolization and for TA100 with metabolization. The measurement of β-galactosidase induction in the SOS-chromotest was positive only for Escherichia coli PQ37 when metabolization enzymes were present. Using Balb/c 3T3 fibroblasts, DNA strand breaks induction by GSE was also investigated by the comet assay and no significative difference was detected for treated and no treated DNA for 60 min. Our data suggest that GSE although no mutagenic presents cytotoxic activity. [Copyright &y& Elsevier]