Experimental cardiovascular depressant effects of garlic (Allium sativum) dialysate.

The objectives of this work were to investigate the effects of a garlic dialysate on diastolic blood pressure (DBP), heart rate (HR) and electrocardiogram (ECG) of anaesthetized dogs and its effects on frequency and tension of isolated rat atria. Garlic dialysate led to a drop in DBP (from 112.5 +/- 3.67 to 70 +/- 3.16 mmHg) and a decrease in HR (from 198 +/- 9.81 to 164 +/- 16.59 beats/min) in a dose-dependent manner. The ECG showed a regular sinus bradycardic rhythm. The addition of garlic dialysate to isolated left rat atria evoked a decrease in tension development. Frequency, measured by spontaneous beating of the right atria, was also reduced. Both effects were dose-dependent. In addition to these effects, the positive inotropism and chronotropism induced by addition of isoproterenol 10(-9) M, were partially antagonized by preincubation of the rat atria with the garlic dialysate. The above findings can be explained by a depressant effect on automaticity and tension development in the heart, suggesting a beta-adrenoceptor blocking action produced by the garlic dialysate.

Anti-arrhythmic profile of a garlic dialysate assayed in dogs and isolated atrial preparations.

The effects of garlic (Allium sativum L., Liliaceae) dialysate were studied on arrhythmias induced in anaesthetized dogs and on isolated left rat atria. Garlic dialysate suppressed premature ventricular contractions (PVC) and ventricular tachycardia (VT) in ouabain-intoxicated dogs as well as the ectopic rhythms induced by isoprenaline (10(-6) M) and aconitine (10(-8) M) on electrically driven left rat atria. The effective refractory period (ERP) and the sinus node recovery time (SNRT) of isolated rat atria were prolonged in a dose-dependent manner by the administration of this extract. Garlic dialysate decreased the positive inotropic and chronotropic effects of isoprenaline in a concentration-dependent manner. These last effects were increased by propranolol. The results suggest that garlic dialysate has a significant antiarrhythmic effect in both ventricular and supraventricular arrhythmias.

Involvement of calcium in the cardiac depressant actions of a garlic dialysate.

In order to elucidate a possible role for calcium on the negative cardiotropic effects of a garlic (Allium sativum L., Liliaceae) dialysate in rat atria we studied: (a) the effects of our extract 15 min after preincubation with high and low concentrations of extracellular calcium ([Ca2+]o) on left and right activity of rat atria. The negative inotropism of garlic dialysate increased with calcium 0.75 mM; in contrast, high level of calcium (4.5 mM) induced a significant reduction of this depressant effect. None of these treatments modified the negative chronotropism of garlic; (b) nifedipine (10(-9) to 10(-7) M, verapamil (10(-9) to 10(-7) M) and diltiazem (10(-9) to 10(-7) M) induced a concentration-dependent synergism of the log concentration-effect of garlic dialysate on left atria. Verapamil and diltiazem (10(-7)M), but not nifedipine increased the inhibitory chronotropism of garlic in right atria; (c) negative inotropic and chronotropic effects demonstrated by nifedipine (1 x 10(-10) to 1.1 x 10(-6) M) were antagonized as expected by preincubation with Bay K-8644. Depressant actions of garlic were not modified with this pretreatment. These results suggest that the negative inotropic effect of our garlic dialysate is related to [Ca2+]o availability. It is possible that a restriction of intracellular calcium contributes to this effect. However, the negative chronotropic effect of garlic is scarcely affected by these modifications.

Direct and indirect effects of ethanol on isometric tension in rabbit isolated strip auricle.

Besides the negative inotropic action of ethanol on cardiac muscle, this paper describes also an "indirect effect" which appears when the ethanol treated isolated strip auricle preparation is washed with low Ca Tyrode solution. This effect depends on the previous concentration of ethanol in the isolated organ bath. A kinetic analysis of the washout effect of ethanol shows that just the first tension diminution phase is altered by the action of ethanol. The results suggest that alcohol may act also on inner membranes of myofibrils.

[Subcellular study of ethanol action on myocardium (author's transl)]. / Estudio subcelular de la acción del ethanol en el miocardio.

The effect of ethanol on calcium binding activity in plasma membrane from dog cardiac muscle is described. The binding activity to sarcolemma was measured by the centrifugation method. The ethanol effect on the activity was studied by measuring the amount of bound calcium when the preparation was incubated in an ethanol containing solution at a desired concentration. Results showed that membrane bound calcium increased with ethanol concentration of up to 180 mM. Higher concentrations only decreased the amount of bound calcium.

Distribution of mast cells and the effect of their mediators on contractility in human myometrium.

OBJECTIVE: To examine the distribution of mast cells in human uterine tissue and to study the interactions between mast cell mediators (histamine and serotonin) and PGF2 alpha in human myometrium contractile activity. DESIGN: Distribution of mast cells were analysed in cryostat sections of myometrium samples stained with Toluidine blue. Contractile activity was evaluated in an isolated organ bath preparation on myometrial strips obtained from women whose pregnancies ended in elective caesarean section. SETTING: Biological Science Laboratories at the University of Concepción. SUBJECTS: Twenty women undergoing elective caesarean and 10 women undergoing hysterectomy at the G. Grant Hospital. MAIN OUTCOME MEASUREMENTS: Cumulative concentration-response curves for histamine and serotonin before and after the addition of subumbral concentrations of the PGF2 alpha or serotonin were performed. RESULTS: Serotonin was more active than histamine to evoke contractions (EC50:0.20 (SE 0.02) mumol/l vs 1.5 (SE 0.2) mumol/l, respectively). Furthermore, threshold concentrations of serotonin (0.05 mumol/l) potentiated the contractile effect of histamine (EC50:0.3 (SE 0.06) mumol/l and 50% increase in E(max)). PGF2 alpha had a poor contractile effect, but threshold concentrations (0.05 and 0.10 mumol/l) enhanced the contractile effect of both serotonin and histamine. A population of mast cells was found in close apposition to smooth muscle fibres. CONCLUSIONS: It is postulated that the simultaneous release of mast cell mediators (histamine and serotonin) in myometrium could be an important stimulus for evoking strong contractions in the human uterus. PGF2 alpha may have indirect effects in myometrium by amplifying the effects of histamine and serotonin.

A single intravenous high dose of cholic acid to a pregnant ewe does not affect fetal well-being.

Cardiovascular variables of both mother and fetus and total bile acid levels were monitored in amniotic fluid and in maternal and fetal plasma after the administration of a single intravenous high dose (29 mg) of cholic acid to a pregnant ewe. We observed the diffusion of significant quantities of cholic acids from the mother to the fetus and amniotic fluid. Nevertheless, cardiovascular parameters (heart rate, blood pressure, PO2, PCO2 and pH) were not affected, neither did intra-amniotic pressure show significant changes compared with the initial experimental conditions. It is concluded that an acute increase in maternal plasma levels of bile acids does not produce important adverse effects in either the mother animal or the fetus and consequently, if bile acids should be deemed responsible for any deleterious effect observed in a preterm fetus in intrahepatic cholestasis, this should be considered as the consequence of a chronic process.

Mast cells mediators evoke contractility and potentiate each other in mouse uterine horns.

1. The ability of prostaglandin F2 alpha (PGF2 alpha), histamine and serotonin to induce and/or potentiate contractions in mouse uterine horns was studied in an attempt to analyze whether uterine mast cells degranulation could favor contractions during labor. 2. PGF2 alpha was the most potent of the three compounds (EC50 = 0.7 microM), being followed by serotonin (EC50 = 1.2 microM) and histamine. Between 10 and 100 microM histamine only evoked weak contractions, not higher than 50% of maximal amplitude of contractions. 3. Serotonin (0.1 microM) potentiated the contractile effect of both histamine and PGF2 alpha when added simultaneously with the corresponding compound to the isolated organ bath. Also, histamine at threshold contractile concentration (3 microM) was able to potentiate the contractile effect of both serotonin and PGF2 alpha. 4. The potentiating effect of PGF2 alpha on both histamine and serotonin evoked contractions was recorded after treating the preparation with 10 microM of the compound for at least 10 min before the corresponding concentration-effect curves were performed. 5. It is postulated that the simultaneous presence of these mast cells mediators in myometrium could be an important stimulus for both to trigger and/or to maintain contractions during labor.

Characterization and distribution of cholinesterase activity in mouse uterine horns: changes in estrous cycle.

1. Both butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) are present in the mouse uterus, BChE being more abundant. 2. Their molecular forms were sequentially solubilized by different extraction media obtaining three ChE fractions whose specific activity was different, depending on the stage of the estrous cycle: hydrosoluble (estrous: 75.5 +/- 6.6 and diestrous: 47.9 +/- 8.7 mU/mg prot); detergent-soluble or amphiphilic (estrous 26.6 +/- 2.4 and diestrous 14.7 +/- 3.3 mU/mg prot.), and high ionic strength-soluble (estrous: 18.7 +/- 4.2 and diestrous 12.8 +/- 1.2 mU/mg prot.). 3. Histochemical procedures demonstrated a different distribution for both ChE activities. AChE was found in nerves next to smooth muscle cells of the circular layer and blood vessels, while BChE was concentrated in the longitudinal stratum surrounding the smooth muscle cells. Under the predominance of progesterone, BChE was also found in the endometrial glands. 4. Maximal contractions evoked by the addition of ACh to the isolated organ bath were concentration dependent and greater in estrous than in diestrous. Nevertheless the difference at the two stages of the estrous cycle disappeared when contractions were normalized to smooth muscle cross-sectional area. 5. BChE but not AChE inhibition augmented maximal contractions elicited by ACh in longitudinal but not in circular smooth muscle. 6. The effect of BChE inhibition on the contractile force developed was greater at lower concentrations of ACh and did not depend on the stage of the estrous cycle.

Efecto de fármacos tocolíticos sobre la actividad contractil evocada por prostaglandinas en el utero gestante / Tocolytic drugs effect in contractil activity evoked by prostaglandines in the pregnant uterus

Se estudió el efecto in vitro de ritodrine (28,7 ng/ml), fenoterol (30,0 ng/ml), verapamil (43 ng/ml), nifedipino (34,6 ng/ml) y sulfato de magnesio (6 meq/lt) sobre la actividad contráctil espontánea y evocada por prostaglandina PGF 2* en cuernos uterinos de ratones con 15 días de gestación. El rango de concentraciones usadas fue cercana a los niveles plasmáticos efectivos alcanzados para cada tocolítico respectivamente. A las dosis señaladas, la actividad contráctil espontánea fue completamente abolida por los tocolíticos investigados. En cambio, las contracciones evocadas por PGF 2* fueron inhibidas solamente por ritodrine, fenoterol y nifedipino. Se discuten posibles mecanismos involucrados en estas interacciones