Involvement of nitric oxide in fading of 5-hydroxytryptamine-induced vasocontraction in rat isolated vena portae smooth muscle.

PURPOSE: The aim of the present study was to investigate a nitric oxide (NO) involvement in the mediation of a 5-HT-induced vasoconstrictions response in the rat portal vein in vitro. MATERIAL AND METHODS: Isolated rat portal vein preparations obtained after dissection were placed in organ baths for isometric force measurement via a strain gauge. RESULTS: 5-hydroxytryptamine (5-HT) in concentrations ranging from 3x10(-8) M to 3x10(-4) M contracted portal vein preparations (EC50= 7x10(-7) M) in a concentration dependent manner. The vasoconstrictions induced by 5-HT was significantly increased in endothelium-denuded vessels. Pre-treatment with N(omega)-nitro-L-arginine methyl Ester (L-NAME 100 microM) enhanced the contractive response to 5-HT either in intact- or denuded endothelium vessels. Whereas, ketanserin (0.1 microM) abolished 5-HT-induced vasoconstrictions (EC50= 4.6x10(-8) M). Furthermore, a non-selective 5-HT receptors agonist, sumatriptan, (1x10(-10 )M - 1x10(-5) M) induced a reduction of spontaneous rhythmic contractions either in endothelium-intact or in endothelium -denuded vessels. However, 5-HT-induced vasoconstriction was unaffected by propranolol (10 microM). CONCLUSIONS: These findings are consistent with the hypothesis that the vasoconstrictor activity of 5-HT in vascular smooth muscle was mediated by activation of 5-HT1B/D and 5-HT2B receptors subtypes involving the endothelium (NO) dependent mechanism.

Leaf extract of Caesalpinia bonduc Roxb. (Caesalpiniaceae) induces an increase of contractile force in rat skeletal muscle in situ.

The pharmacological properties of Caesalpinia bonduc Roxb. (Caesalpiniaceae) are not well known, but it is used traditionally to treat snake bite (Bellomaria and Kacou, 1995; Schaffner, 1997). In the present study, the mechanism through which Caesalpinia bonduc extract (Cebo) affects gallamine-induced relaxation in rat tibial muscle contractility were studied via measurement of isometric-tension-anesthetized, 10-12-week-old, male rats. Isometric twitch contractions of the indirectly-stimulated anterior tibia muscle of the right hindleg were recorded in situ. Cebo administered intravenously (i.v.) increased twitch contractions in a dose-dependent manner. The ED50 value is 2.75 x 10(-4) g/kg body wt. Similar results were obtained using the anticholinesterase neostigmine. In contrast, gallamine (a non-depolarizing muscle relaxant) or the venom of the puff adder Bitis arietans reduced the force of contraction. Treatment with Cebo or neostigmine, however, reversed the relaxation induced by either gallamine or puff adder venom. In conclusion, Cebo stimulates the muscle contractile activity, an effect which may be due to an activation of the cholinergic mechanism.

Pharmacological investigation on nigrescigenin-a cardenolide from Parquetina nigrescens (Afzel.) Bullock: comparative studies on cardiotonic effects of Parquetina nigrescens, g-strophanthin and noradrenaline in guinea-pig isolated atria.

The cardiotonic and catecholamine-like effects of Parquetina nigrescens extract-induced contractile force of guinea-pig left and right atria were investigated in-vitro. Isometric contractions were recorded. P. nigrescens extract, 5-150 microg mL(-1), increased the force of contraction dose dependently in electrically driven left atria. The concentration of P. nigrescens extract producing 50% of the maximal effect (EC50 value) was 7.5 microg mL(-1). The positive inotropic response differed from that of g-strophanthin by its high rate of onset and its complete reversibility upon removal of the extract from the incubation medium. In spontaneously beating right atrial muscle, P. nigrescens extract increased the rate of contractions. Its positive chronotropic and inotropic effects were partly antagonized by propranolol and atenolol indicating the presence of an adrenergic acting principle in P. nigrescens extract. In contrast, the inotropic response to P. nigrescens extract could not be completely suppressed by beta-blocking agents, suggesting that the force of contraction is not only increased by a sympathomimetic ingredient of P. nigrescens extract but also by the cardenolides known to be present in P. nigrescens.

At receptor inhibition affects the noradrenaline sensitivity in isolated portal vein of normotensive rat.

Short term treatments of normotensive Wistar Kyoto rats with angiotensin II (ANGII) or in combination with the AT1 receptor antagonist, losartan or PD123319, the AT2 receptor antagonist on systemic arterial blood pressure (MABP) and their influence on noradrenaline sensitivity in isolated mesenteric portal vein were evaluated. ANGII increased MABP as well as the contractile response to noradrenaline in vessels from ANGII-treated animals. MABP and the maximal effect of the concentration response curve for noradrenaline were prevented by losartan. However, PD123319 did not influence the blood pressure, but completely removed the vessels sensitivity to noradrenaline. ANGII combined with the AT1 and/or AT2 receptors blockade completely prevented the pressure response to ANGII, but the concentration response curve for noradrenaline did not differ from the vehicle-treated control curve. In conclusion both AT1- and AT2 receptor activation seems to be important in controlling noradrenaline sensitivity of rat portal vein smooth muscle.

Short treatments of normotensive and hypertensive rats by angiotensin II and nitric oxide inhibitor induce an increase of noradrenaline sensitivity in isolated vena portae preparations.

The aim of the study was to examine the influence of a short-term treatment of conscious Wistar Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) by angiotensin II (ANG II) and by ANG II in combination with either l -NAME, HOE 140 or minoxidil on the mean arterial blood pressure (MABP) and the noradrenaline sensitivity in isolated portal vein preparations. MABP was significantly increased by ANG II treatment and ANG II plus l -NAME. However, it was slightly affected by ANG II in association with HOE 140, and significantly lowered by ANG II plus minoxidil. In control animals noradrenaline increased the frequency and the tone of contractile force. While ANG II enhanced the contractile response to noradrenaline, neither in combination with l -NAME, HOE 140 nor minoxidil prevented such an increase in the response to noradrenaline. In the presence of ergotamine, the contractile response to noradrenaline was completely blocked not only in control animals, but also in animals treated with ANG II alone or in combination with minoxidil. However, ergotamine (3 microm) failed to block completely the contractile response to noradrenaline in vessels from animals treated by ANG II in combination with l -NAME or HOE 140. These data suggest that ANG II causes an increase of noradrenaline sensitivity in the isolated portal vein of rat. l -NAME and HOE 140 unmask a contractile response to noradrenaline in the presence of ergotamine which seems to be mediated not only by alpha-adrenoceptors, but may be compensated by an endothelial relaxation.

Sympathomimetic effects of Parquetina nigrescens (Periplocaceae) extract in isolated portal vein smooth muscle.

The purpose of this study was to examine the mechanisms underlying the pharmacological effects of the extract of Parquetina nigrescens (Expar) on vascular smooth muscle contractility. To evaluate the Expar effect, the contractile activity of portal veins isolated from Wistar Kyoto rats was isometrically recorded. Isolated portal vein preparations developed rhythmic and spontaneous contractile activity. Expar increased the contractile response of the portal vein preparations in a dose-dependent manner. The maximal effect of the dose-response curve for Expar was prevented by the alpha1-adrenergic blocking agent prazosin at 10 nM and 30 nM concentration dependently. The contractile responses of the muscle to Expar were partly blocked after chemical sympathectomy of the preparations with 6-hydroxydopamine, and those obtained in the same conditions with tyramine were completely abolished, whereas responses to noradrenaline were unaffected by the 6-hydroxydopamine pretreatment. It is concluded that Expar contains principles, which can be characterized as direct and indirect sympathomimetic.

Effects of leaf extract of Caesalpinia bonduc (Caesalpiniaceae) on the contractile activity of uterine smooth muscle of pregnant rats.

The calcium dependency and the cholinergic effect of the leaf extract of Caesalpinia bonduc Roxb. (Caesalpiniaceae) was studied in isolated pregnant rat myometrium preparations. Isometric contractions were recorded. The extract (Cebo) increased the contractile force in the isolated strips in a concentration-dependent manner. The effects were comparable to those obtained with acetylcholine. Contractions induced by Cebo or acetylcholine were inhibited in the presence of atropine. The stimulating action of Cebo on the contractile responses of isolated myometrium preparations inhibited by atropine may be mediated by cholinergic receptors. In calcium-free solution Cebo induced a tonic contraction (contracture) of the muscle. Moreover, in high-potassium calcium-free solution Cebo caused contracture of the uterine smooth muscle. Cebo was still able to elicit contractions in calcium-free solution containing EDTA or EGTA. These findings suggest the existence of cholinergic receptors sensitive to Cebo which could influence the influx of calcium (phasic contraction) and mobilization of calcium from cellular stores (tonic contraction), both of which are responsible for the increase of contractile activity and development of the contracture of uterine smooth muscle.