Quercetin, one of the most widely distributed flavonoids in the plant kingdom, inhibits various enzymes. This study examined its inhibitory effect on the angiotensin-converting enzyme activity through the cardiovascular response to bradykinin and angiotensin I. Quercetin pretreatment (88.7 µmol/kg p.o., 45 min; 14.7 µmol/kg i.v., 5 min) significantly potentiated the hypotensive effect of bradykinin (10 nmol/kg i.v.). This association was significantly attenuated by an antagonist of the B2 receptor. In addition, the hypertensive response to angiotensin I (0.1 nmol/kg i.v.) was significantly reduced by quercetin pretreatment using the same parameters as before. These results suggest an inhibitory effect of quercetin on the angiotensin-converting enzyme activity, similar to that of captopril. Quercetin was equally effective when given orally or intravenously.

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A crude aqueous alcoholic extract of Mandevilla velutina (Apocynaceae) rhizomes produced a concentration-dependent displacement to the right of the concentrationresponse curve to bradykinin (Bk) in the isolated uterus of the rat. Schild analysis of the data revealed a linear relationship (r = 0.99) and yielded a pA2 value of 3.3 + 0.08 (-log g ml-') but the slope differed significantly from unity. The anti-Bk action was of rapid onset and was reversible upon washout. Contractions induced by acetylcholine, oxytocin, angiotensin II and BaCl2 were unaffected by the extract. This represents the first report of a selective Bk antagonist of plant origin. The isolation of the active principle(s) may result in a useful pharmacological tool for elucidating the physiological and physiopathological roles of endogenous Bk.

The effect of a fraction (Bc2) from the venom of the sea anemone Bunodosoma caissarum on [3H]glutamate release from rat cortical synaptosomes was investigated. Bc2 (2-20 microg/ml) provoked massive glutamate release without causing synaptosome disruption. Glutamate release stimulated by Bc2 was independent of extracellular Ca2+ and of voltage-sensitive Na+ channels, and it was completely abolished by the addition of sphingomyelin. No definitive evidence about the mechanism underlying the stimulatory effect of Bc2 is available as yet. However, a direct interaction with the exocytotic machinery cannot be ruled out.

Tannins are common constituents of medicinal plant crude extracts and have been reported to have pharmacological actions of their own. Studies on these actions are likely to be helpful in interpreting data obtained with tannin-rich crude plant extracts. In this context, the present report analyses the effects of tannic acid on responses of the isolated rat uterus and vas deferens to agonists and left atrium to electrical stimulation, as well as on blood pressure in anesthetized rats. Tannic acid dose-dependently and non-competitively antagonized contractions to different agonists in rat uterus and vas deferens. The compound produced a biphasic effect in the atrium. Whereas lower concentrations (30 to 100 wg/ml) enhanced inotropism, higher concentrations (>300 sglml) promoted depression of contractility. Intravenous tannic acid led to hypotension, which was partially reduced by antihistamine pretreatment, but did not affect heart rate. The depressant effect of tannic acid in uterine fragments was potentiated by increasing calcium concentration in the bathing solution, although in the depolarized strips the compound non-competitively antagonized calcium-induced contractions. The results suggest that tannic acid can affect calcium availability for contraction of smooth and cardiac muscles. This action could well mask the effects of other active constituents of tannie-rich plant extracts. Isolated uterus Uterine strips, 15-20 mm long, were suspended in 10 ml of aerated de Jalon solution (composition in mM: NaCI 154, KCI 5.

The purpose of the present experiments was to study the effects of various neurokinin related peptides, such as substance P, [beta Ala8]NKA(4-10), and [MePhe7]NKB, which are selective for NK-1, NK-2, and NK-3 functional sites, respectively, to induce plasma extravasation in rats and the effectiveness of RP 67580 and CP-96,345 (two nonpeptide NK-1 receptor selective antagonists) and SR 48968 (a nonpeptide NK-2 receptor selective antagonist) to prevent such an effect. Bolus intravenous injection of substance P (1.0 nmol/kg) into conscious rats induced extravasation of Evans blue dye (EB), a selective marker of albumin vascular permeability, in the duodenum, the stomach, the pancreas, and the urinary bladder by 50, 40, 58, and 312%, respectively; a slight increment occurred also in the ileum and the kidney but was not significant. [beta Ala8]NKA(4-10) (1.0 nmol/kg) increased EB extravasation in the stomach and the urinary bladder by 52 and 99%, respectively, while [MePhe7]NKB (1.0 nmol/kg) did the same in the stomach, the ileum, and the urinary bladder by 58, 50, and 79%. Pretreatment with RP 67580 (250 nmol/kg) blocked the albumin extravasation mediated by substance P in the duodenum, the pancreas, and the urinary bladder by 100, 100, and 78%, respectively. CP-96,345 (250 nmol/kg) also inhibited EB extravasation mediated by substance P in the duodenum and the pancreas by 100 and 100%, respectively, but was ineffective in the urinary bladder. Neither RP 67580 nor CP-96,345 prevented the substance P mediated extravasation in the stomach. RP 67580 and CP-96,345 did not antagonize the effects of NK-2 and NK-3 selective agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

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1The effect of four semi-purified compounds obtained from Mandevilla velutina crude extract by silica gel chromatography fractionization were analysed for their inhibitory effects on uterine contractions induced by bradykinin (BK), lysylbradykinin (L-BK), acetylcholine (ACh) and oxytocin, in vitro.2 None of the compounds tested affected uterine tone. Pre-incubation for 20 min with fraction 12 (20 to 80plgmlm'), isolated from M. velutina produced a parallel and concentration-dependent displacement to the right of the concentration-response curves for BK and L-BK (1 to 1000 nM). Schild plots of these data were linear (correlation close to unity), and yielded a nominal pA2 value (as g ml-') of 5.1 and 4.9, respectively, and the values of the slopes were not significantly different from unity. Fraction 11 (10 to 40 ptg ml-') also produced a parallel and concentration-dependent displacement to the right of the BK concentration-response curve. The Schild plot gave a mean pA2 value (g ml-') of 5.4 and a slope not significantly different from unity. 3 Fraction 12 did not influence the uterine contractile responses induced by ACh (0.1 to 100gM) and oxytocin (0.01 to 30 miu ml-') at concentrations less than 80 pg ml-'.4 Fraction 16 (20 to 80 gml-') antagonized the action of BK only at concentrations greater than 40 ggml', whereas fraction 5 (20 to 80 ggml1') was completely inactive against BK-induced responses.5 As observed previously with the crude extract, the onset of the BK antagonistic action of these compounds was rapid and completely reversible following intermittent washing of the preparation for 30-60 min. 6 These results indicate the existence of at least two compounds in the crude extract of Mandevilla velutina that act as competitive and selective kinin antagonists on the isolated uterus of the rat.