P1A recombinant beta-lactamase prevents emergence of antimicrobial resistance in gut microflora of healthy subjects during intravenous administration of ampicillin.

Ipsat P1A is a recombinant beta-lactamase which degrades antibiotic residue in the gastrointestinal tract. In an open-label, single-center controlled trial, 36 healthy subjects were randomized to receive (i) ampicillin (1 g intravenously [i.v.

Involvement of Rho kinase pathway in the mechanism of renal vasoconstriction and cardiac hypertrophy in rats with experimental heart failure.

Rho-dependent kinases serve as downstream effectors of several vasoconstrictor systems, the activities of which are upregulated in congestive heart failure (CHF). We evaluated renal and cardiac effects of Y-27632, a highly selective Rho kinase inhibitor, in an experimental model of volume-overload CHF. Effects of acute administration of Y-27632 (0.

Renal effects of 2-mercaptoacetyl-L-leucyl-L-phenylalanine, a novel selective inhibitor of neutral endopeptidase 24.11 (Neprilysin): comparison with SQ 28,603.

The effects of 2-mercaptoacetyl-L-leucyl-L-phenylalanine (MA-LF) on the activity of neutral endopeptidase and on renal hemodynamics and excretory function were investigated in experiments in vitro and in vivo. In vitro studies showed that the compound effectively inhibited purified bovine kidney neutral endopeptidase (Ki = 0.012 microM), while having slight influence on the activity of angiotensin I converting enzyme (Ki = 0.

Effects of eprosartan on renal function and cardiac hypertrophy in rats with experimental heart failure.

Activation of the renin-angiotensin system may contribute to the derangement in renal and cardiac function in congestive heart failure. The present study evaluated the effects of eprosartan, a selective angiotensin II receptor antagonist, on renal hemodynamic and excretory parameters and on the development of cardiac hypertrophy in rats with aortocaval fistula, an experimental model of congestive heart failure. Infusion of eprosartan (1.

Regulation of intrarenal blood flow in experimental heart failure: role of endothelin and nitric oxide.

Congestive heart failure(CHF) is associated with a marked decrease in cortical blood flow and preservation of medullary blood flow. In the present study we tested the hypothesis that changes in the endothelin (ET) and nitric oxide (NO) systems in the kidney may contribute to the altered intrarenal hemodynamics in rats with aortocaval fistula, an experimental model of CHF. Cortical and medullary blood flow were measured simultaneously by laser-Doppler flowmetry in controls and rats with compensated and decompensated CHF.

Impaired nitric oxide-mediated renal vasodilation in rats with experimental heart failure: role of angiotensin II.

Background: Congestive heart failure (CHF) is associated with a decrease in renal perfusion. Because endothelium-derived NO is important in the regulation of renal blood flow (RBF), we tested the hypothesis that an impairment in the NO system may contribute to the decrease in RBF in rats with experimental CHF.

Methods And Results: Studies were performed in rats with experimental high-output CHF induced by aortocaval (AV) fistula and sham-operated controls.

[The effect of verapamil on cardio- and hemodynamics in rats with various models of hypertension].

Rats with various models of hypertension (spontaneous, renal, neurogenic, adreno-regenerative) were used in experiments to study the effect of verapamil on parameters of cardio- and hemodynamics in its two-week oral administration. The antihypertensive effect of verapamil was most expressed in rats with spontaneous model of hypertension and initial hyperkinetic variant of circulation.

Differential regulation of renal regional blood flow by endothelin-1.

The present study evaluated the effects and mechanisms of action of endothelin-1 (ET-1) on medullary and cortical blood flow (MBF and CBF, respectively). CBF and MBF were measured simultaneously by laser-Doppler flowmetry in anesthetized male Wistar rats. Bolus injection of ET-1 (1.

Bosentan improves renal regional blood flow in rats with experimental congestive heart failure.

The effects of the mixed endothelin receptor antagonist bosentan on renal regional haemodynamics were investigated in rats with aorto-caval fistula, an experimental model of congestive heart failure. A matched group of normal rats served as control. Injection of bosentan (10 mg/kg i.

Urinary neutral endopeptidase 24.11 activity: modulation by chronic salt loading.

Neutral endopeptidase (NEP) 24.11 is a zinc-metallopeptidase involved in the metabolism of several biologically active peptides including enkephalin, atrial natriuretic peptide, bradykinin, and endothelin. The enzyme is found in abundant amounts in the brush border of renal proximal epithelial cells.

Renal effects of big endothelin-1 in experimental congestive heart failure.

The present study was designed to evaluate the effects of big endothelin (ET) on renal hemodynamics and excretory functions in rats with experimental congestive heart failure (CHF) produced by aortocaval fistula. Clearance studies were performed in control and in chronic (7 day) CHF rats. Administration of bit ET (1 and 3 nmol/kg, i.

Differential effect of endothelin-1 on renal regional blood flow: role of nitric oxide.

This study evaluated the effects of endothelin-1 (ET-1) on medullary and cortical blood flow (MBF and CBF, respectively) and the interactions with other local vasoactive systems in the regulation of renal regional blood flow. CBF and MBF were measured simulataneously by laser-Doppler flowmetry in anesthetized Wistar rats. Administration of ET-1 (1.

[The anti-ischemic properties of crown ether derivatives].

Experiments on open-chest anaesthetized cats were made to test derivatives of crown ethers, such as benzylase-15-crown-5 and dibenzylase-15-crown-5 for their effects on myocardial ischemia and the functional status of a myocardial ischemic focus in temporary coronary occlusion during coronary spasm induced by dihydroergotamine and during coronary microthrombosis caused by ADP. When intravenously administered in doses of 0.5-15 mg/kg, the tested agents were found to enhance myocardial tolerance to ischemia, depressed ST segment in ischemia induced by coronary occlusion and administration of ATP, and prevented ST-segment depression during coronary spasm.

[The relationship between the magnitude of the negative inotropic action and chemical structure of crown-ether derivatives].

The relationship between the inotropic effect and chemical structure of 15-crown-5 and 18-crown-6 derivatives was studied in experiments in open-chest anaesthesized cats, by using computer-aided analysis. The findings showed that the 15-crown-5 derivatives produced more pronounced cardiotropic effect and they were less toxic than 18-crown-6 derivatives. Computer-aided analysis revealed pharmacophoric groups which are responsible for cardiotropic (negative inotropic) activity in the series of crown ether derivatives.

[The effect of a crown-ether derivative, ethmozine and etatsizin on the functioning of the calcium pools in the guinea pig myocardium].

Analysis of the component structure of single contractions of papillary muscles in guinea pigs was used to study the effects of the crown ether derivative benzylase-15-crown-5 and the antiarrhythmic agents ethmozine and ethacizine. The negative inotropic effect of these compounds was shown to be associated with limited penetration of calcium ions from the sarcolemmal pool into cardiac cellular myoplasm.

Investigation of antiischemic properties and mechanism of action of azacrown ether derivative.

The influence of the azacrown ether derivative benzylaza-15-crown-5 on myocardial tolerance to ischemia and on the functional state of the zone of myocardial ischemia during coronary artery occlusion was investigated in experiments on anaesthetized open-chest cats. The compound tested produced a dose-dependent antiischemic effect and prevented the development of myocardial ischemia. In experiments on isolated guinea-pig papillary muscle benzylaza-15-crown-5 inhibited the first and second components of the isoproterenol-induced muscle contraction.

[A comparative evaluation of the anti-ischemic action of verapamil in different models of myocardial ischemia].

The effectiveness of the anti-ischemic effect of verapamil was studied on models of coronary spasm (the test with dihydroergotamine) and microthrombosis of the coronary arteries (the test with ADP). The results of the performed studies showed that verapamil exerts the anti-ischemic effect at administration of dihydroergotamine and ADP. The most pronounced effect of verapamil was demonstrated on the model of myocardial ischemia due to coronary spasm.

[The anti-ischemic properties of verapamil and its effect on myocardial functional potentials in coronary artery occlusion].

The effect of verapamil on the functional state of the ischemic myocardium, the myocardial tolerance to ischemia and the processes of urgent adaptation of the heart in the coronary artery occlusion was investigated in the experiments on anesthetized open-chest cats. Verapamil was shown to exert the dose-dependent anti-ischemic action, to increase the myocardial tolerance to ischemia, to suppress the response to the physiological saline infusion and not to change adrenoreactivity of the ischemic myocardium at the coronary artery compression.

[An experimental study of the cardio- and hemodynamic effects of the carboxyl ionophore monensin].

The effect of ionophore monensin on the main parameters of cardio- and hemodynamics was studied in the experiments on anesthetized cats. Monensin (0.075-0.

[Mechanism of the vascular action of verapamil and a crown ether derivative].

The effects of verapamil and benzyl-aza-15-crown-5 on pressor reactions of blood pressure and perfusion pressure in the femoral artery after administration of noradrenaline, tyramine, angiotensin amide and stimulation of the femoral nerve were studied in acute experiments on anesthetized cats (pentobarbital sodium, 50 mg/kg). Verapamil (0.5 mg/kg) and benzyl-aza-15-crown-5 (9 mg/kg) suppressed pressor reactions to the nerve stimulation and produced no changes at administration of noradrenaline, tyramine and angiotensin amide.

[Cardio- and hemodynamic effects of a crown ether derivative and an analysis of its cardiotropic action in an experiment].

The cardio- and hemodynamic effects of the derivative of aza-15-crown-5 was studied in acute experiments on anesthetized (ethaminal sodium, 50 mg/kg) cats. At intravenous administration the compound was found to induce hypotension, to dilate arterial vessels, to exert negative ino- and chronotropic effects, to decrease the cardiac output. The pharmacological analysis suggests that the mechanism of the cardiotropic action of the compound is due to its intervention in calcium ion metabolism.

[Effect of tranquilizers on myocardial function in stress injury].

Experiments on rats were performed to evaluate the action of diazepam (1 mg/kg), phenazepam (1 mg/kg), meprotan (25 mg/kg), mebicar (500 mg/kg), and phenibut (25 mg/kg) on myocardial function under stress-induced injury. Diazepam, phenazepam and phenibut protected the myocardium from stress by raising the functional reserves of the heart. Meanwhile meprotan and mebicar produced no stress-protective action on the heart under similar conditions.

[Effect of tranquilizers on the course of myocardial ischemia and on myocardial resistance to hypoxia in coronary artery occlusion].

It was shown that meprobamate and phenazepam protect the myocardium from hypoxia and decrease myocardial ischemia during coronary occlusion. Phenibut and mebicar reduce the tolerance to ischemia and increase the degree of ischemic injury to the heart. Diazepam has no effect on these processes.