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C Ribuot

Publications and source records attributed to C Ribuot.

50 records · Page 3Linked to original sources
PubMed1996

Skeletal muscle beta-adrenoreceptors and phosphate metabolism abnormalities in heart failure in rats.

To investigate the mechanisms leading to skeletal muscle metabolic abnormalities in chronic heart failure (CHF), we studied phosphate metabolism and skeletal muscle beta-adrenoreceptors (beta-AR) in rats 12-14 wk after coronary ligation (CL). We performed 31P magnetic resonance spectroscopy in the gastrocnemius muscle during motor activity produced by electrical stimulation (5 Hz). The initial slope of phosphocreatine (PCr) depletion was higher in the CL rats compared with sham-operated rats (Pi/PCr/time: 0.211 +/- 0.045 vs. 0.113 +/- 0.029; P < 0.05). During recovery, both PCr resynthesis rate and maximal rate of oxidative ATP synthesis were reduced threefold in the CL rats compared with controls (11 +/- 2 vs. 37 +/- 7 mmol.l-1.min-1, P < 0.04; and 20 +/- 3 vs. 79 +/- 18 mmol.l-1.min-1, P < 0.03, respectively). There were no significant differences either for the skeletal muscle density (13 +/- 6 vs. 15 +/- 3 fM/mg) or for the affinity (0.244 +/- 0.149 vs. 0.246 +/- 0.146 nM) of beta-AR between the two groups. This study showed that, although in moderate CHF skeletal muscle metabolic abnormalities can be demonstrated, these changes could not be explained by skeletal muscle beta-adrenergic receptor alterations in this experimental model.

Animals↗
PubMed1994

Negative chronotropic effect of the atrial natriuretic peptide in an anesthetized dog model.

The effects of atrial natriuretic peptide (ANP) on heart rate and on the chronotropic response induced by angiotensin II were evaluated. The action of angiotensin II, injected into the sinus node artery, on heart rate was determined in anaesthetized and vagotomized dogs pretreated with beta-adrenoceptor antagonist (n = 9), before and after the infusion of physiological and pharmacological doses (10 and 50 ng/kg per min) of ANP. ANP plasma concentrations were determined by radioimmunoassay. Compared to the baseline concentration values (117 +/- 3 pg/ml), a slight increase was produced by the lower dose (293 +/- 45 pg/ml), whereas a significant augmentation was noted with the higher dose of ANP (1024 +/- 255 pg/ml). The basal heart rate and mean systemic arterial pressure were decreased (26.3 and 13.5%) during the intravenous infusion of the physiological dose of the peptide and were significantly reduced (32.5 and 29.2%, P < 0.05) by the administration of the pharmacological dose of ANP. Angiotensin II had a positive chronotropic effect (29 +/- 3 beats/min) that was significantly inhibited by the pharmacological dose of ANP. Our results suggest that ANP might have a role in the control of heart rate.

Adrenergic beta-Antagonists↗
PubMed1994

Prolongation by captopril of action potential duration in the normal and hypertrophied rat ventricle: direct action or inhibition of the local angiotensin converting enzyme?

OBJECTIVE: The aims were: (1) to study the acute effects of captopril on the action potential characteristics of ventricular fibres from the normal rat, (2) to compare the effects of captopril with those of perindoprilat, a non-thiol angiotensin I converting enzyme (ACE) inhibitor, (3) to determine the electrophysiological properties of the peptide substrates of converting enzyme, bradykinin and angiotensin I, and (4) to investigate whether the effects of captopril occurring in the healthy heart also occur in two models of ventricular hypertrophy. METHODS: Action potentials were recorded with the standard glass microelectrode technique in right ventricular preparations excised from rat hearts and superfused under baseline conditions and with drug containing or peptide containing Tyrode solution. Ventricular hypertrophy was induced in response to hypertension (unilaterally nephrectomised, DOCA-salt model) or 4 week old left ventricular infarction. RESULTS: In preparations from normal rat hearts, captopril increased action potential duration in a concentration dependent fashion [EC50 = 3.5 x 10(-8) M; maximum effect = 44(SEM 5.1)% prolongation at 10(-5) M for action potential duration at 90% repolarisation, APD90]. Perindoprilat similarly caused a dose dependent increase in action potential duration, but with 100 times greater potency [EC50 = 3.1 x 10(-10) M; maximum effect = 71(11)% prolongation at 10(-5) M for APD90]. SQ 14,534, a stereoisomer of captopril with one hundredth the ACE inhibitor potency, had no significant effect on action potential duration at 10(-5) M. Angiotensin I and bradykinin caused concentration dependent prolongation of action potential, but angiotensin II (10(-6) M) had no effect. Captopril (10(-5) M) had no significant effect in the hypertrophied right ventricle from DOCA-salt hypertensive rats, but significantly increased APD90 [39(4.9)%] in right ventricular preparations from rats with 4 week old anterior left ventricular infarction. CONCLUSIONS: In the rat, captopril prolongs action potential duration, an effect possibly due to local accumulation of bradykinin and angiotensin I.

Action Potentials↗
PubMed1994

Intracoronary infusion of bradykinin: effects on noradrenaline overflow following reperfusion of ischemic myocardium in the anesthetized dog.

OBJECTIVE: The aim of this study was to investigate the effects of intracoronary bradykinin (BK) infusion on noradrenaline release and ventricular arrhythmias induced by coronary occlusion and reperfusion in the anesthetized dog. METHODS: 14 anesthetized adult mongrel dogs of either sex underwent a 60 min occlusion of the left anterior descending coronary artery (LAD) followed by a 30-min reperfusion period. BK (1 ng.kg-1.min-1, n = 7), or its vehicle (Lactate Ringer, n = 7), infusions just distal to the left coronary ostium started 15 min before the LAD occlusion and were maintained throughout the experimental period. An epicardial vein, running parallel to the LAD was cannulated to enable the biochemical determinations. The effects of BK on ventricular arrhythmias, cardiac noradrenaline and lactate releases and creatine kinase activity were assessed. RESULTS: BK significantly reduced the amount of noradrenaline released at reperfusion by ischemic myocardium (from 82.1 +/- 31.7 to 11.9 +/- 9.6 ng.min-1), as well as plasma creatine kinase activity at 30 min of reperfusion. This is accompanied by a significant reduction in the incidence of reperfusion-induced sustained ventricular tachycardia. CONCLUSION: This suggests that the protective effect of bradykinin against reperfusion-induced sustained ventricular tachycardia could be associated with a reduction in cardiac noradrenaline release.

Animals↗
PubMed1994

Early incidence of adriamycin treatment on cardiac parameters in the rat.

To evaluate the early effect of low doses of adriamycin (ADR) on cardiac parameters, male Wistar rats were injected with ADR (1 mg.kg-1.day-1) or saline for 10 days. Seven days later, T1 and T2 relaxation times were determined in left ventricular (LV) free wall, septum, and thigh muscle samples. In another experiment, performed on isolated working hearts of rats pretreated with ADR, LV performance was determined along with an index of myocardial lipid peroxidation in this tissue. Lipid peroxidation was enhanced (p < 0.05). This change was not associated with a reduced LV performance, since both aortic and cardiac flows measured in working heart preparations were similar between control and treated rats. However, the coronary flow was significantly reduced (control group, 21 +/- 1 mL.min-1.g-1, ADR group, 15 +/- 1 mL.min-1.g-1; p < 0.001). T1 increased in the LV free wall (665 +/- 3 to 696 +/- 5 ms, p < 0.001) and in the septum (657 +/- 3 to 696 +/- 5 ms, p < 0.01), while T2 increased only in the LV free wall (50.8 +/- 0.9 to 53.1 +/- 0.6 ms, p < 0.05). Myocardial water content was also significantly increased. No modification was observed in the thigh muscle samples. Thus, modifications of T1 and T2 relaxation times following ADR treatment are associated with biochemical changes implicating lipid peroxidation. These changes in relaxation times appeared earlier than hemodynamic deterioration and could provide a basis for the application of proton nuclear magnetic resonance imaging in the early detection of cardiac ADR toxicity.

Animals↗
PubMed1993

Mediation by B1 and B2 receptors of vasodepressor responses to intravenously administered kinins in anaesthetized dogs.

1. Vasodepressor responses to intravenous (i.v.) injection of bradykinin (BK) and des-Arg9-BK, a selective B1 kinin receptor agonist, were characterized following i.v. pretreatment with selective B1 ([Leu8]-des-Arg9-BK) and B2 (Hoe 140) kinin receptor antagonists in anaesthetized dogs. 2. Des-Arg9-BK (0.05-3.3 nmol kg-1) produced dose-dependent decreases in mean arterial blood pressure with a ED50 0.4 nmol kg-1. The vasodepressor effects evoked by des-Arg9-BK (0.6 nmol kg-1) and BK (0.2 nmol kg-1) were greater after i.v. and i.a. injections, respectively. 3. The vasodepressor response to BK (0.6 nmol kg-1) but not to des-Arg9-BK (0.6 nmol kg-1) was significantly (P < 0.001) blocked by pretreatment with the B2 receptor antagonist, Hoe 140. 4. The vasodepressor response to des-Arg9-BK (0.6 nmol kg-1) but not to BK (0.6 nmol kg-1) was significantly (P < 0.001) reduced by pretreatment with the selective B1 receptor antagonist, [Leu8]-des-Arg9-BK. Although both B1 and B2 receptor antagonists caused a transient fall in blood pressure, their inhibitory action was unlikely to be related to a desensitization mechanism. 5. Inhibition of prostaglandin synthesis with indomethacin prevented the vasodepressor response induced by arachidonic acid (1 mg kg-1, i.v.) but not that to BK or des-Arg9-BK (0.6 nmol kg-1). 6. These results suggest, firstly, that the vasodepressor responses to i.v. BK and des-Arg9-BK are mediated by the activation of B2 and B1 receptors, respectively; secondly, that prostaglandins are not involved in the vasodepressor responses to kinins.These findings provide pharmacological evidence for the existence of functionally active B1 receptors in canine cardiovascular homeostasis.

Anesthesia↗
PubMed1993

In vivo B2-receptor-mediated negative chronotropic effect of bradykinin in canine sinus node.

The chronotropic response to bradykinin (BK) injected into the sinus node artery was evaluated in anesthetized dogs. The animals (n = 14) were vagotomized and pretreated with propranolol (1 mg/kg i.v.) to prevent baroreceptor-mediated effects. Dose-dependent decreases in heart rate (from 2.4 +/- 1.3% for 1 microgram of BK to 13.1 +/- 3.7% for 10 micrograms of BK), as well as a significant fall in systemic systolic and diastolic blood pressures, were observed. Captopril (2 mg/kg i.v.) caused significant decreases in systolic (from 117 +/- 11 to 77 +/- 12 mmHg, P < 0.001) and diastolic (from 87 +/- 8 to 52 +/- 8 mmHg, P < 0.001) blood pressures but had no effect on heart rate. Converting-enzyme inhibition potentiated the BK-induced bradycardia. The new potent B2-receptor antagonist, HOE 140 (100 micrograms), significantly blocked the BK-induced chronotropic effect, whereas desArg9-BK, a B1-receptor agonist, was without effect. Prostaglandin involvement was excluded, since pretreatment with indomethacin did not prevent the bradycardia. In conclusion, in vivo BK induces a direct negative chronotropic effect, which is potentiated by converting-enzyme inhibition and is mediated by the B2-receptors independently of the prostaglandins.

Adrenergic beta-Antagonists↗
PubMed1992

Intracoronary administration of saralasin: effects on cardiac arrhythmias induced by ischaemia and reperfusion in the anaesthetised dog.

OBJECTIVE: The aim was to study (1) the effects of intracoronary saralasin, an angiotensin II receptor antagonist, on ischaemia induced and reperfusion induced regional cardiac noradrenaline release and ventricular arrhythmias; and (2) the implication of angiotensin II in coronary constriction during myocardial ischaemia. METHODS: Eighteen adult mongrel dogs, weight 22.6(SD 1.1) kg, anaesthetised with sodium pentobarbitone, were used for the study. The left anterior descending coronary artery was ligated for 60 min and then reperfused for 30 min. Saralasin (60 micrograms.kg-1, n = 9) or its vehicle (Ringer lactate, n = 9) was injected into the artery at the beginning of the occlusion period. Two epicardial veins, one running parallel to the left anterior descending coronary artery and the other parallel to the circumflex coronary artery, were cannulated for the measurement of their respective blood flows and of noradrenaline, lactate, and creatine kinase release. RESULTS: Saralasin decreased the incidence of ventricular fibrillation during coronary occlusion (from 44% in the vehicle treated group to 0% in the saralasin treated group, p = 0.0412). This effect was accompanied by significant vasodilatation in both epicardial veins during myocardial ischaemia. Neither the increases in noradrenaline, lactate, and creatine kinase release nor the incidence and duration of the ventricular arrhythmias following reperfusion were modified by the administration of saralasin. CONCLUSIONS: Intracoronary saralasin in the early phase of myocardial ischaemia increases the epicardial venous blood flow significantly, suggesting that angiotensin II is implicated in coronary constriction during ischaemia. This haemodynamic effect is accompanied by a significant decrease in the incidence of ventricular fibrillation. However, the renin-angiotensin system does not appear to be implicated in the reperfusion induced noradrenaline release nor in the incidence of the ventricular arrhythmias.

Animals↗
PubMed1991

Reduction of tissue noradrenaline content in the isolated perfused rat heart during ischemia: importance of monoamine oxidation.

The effect of ischemia on myocardial noradrenaline concentration and endogenous noradrenaline output was studied in the isolated perfused rat heart. Following a 15-min stabilization period, regional ischemia was produced by coronary artery ligation. After 60 min of ischemia, noradrenaline concentrations were significantly reduced in the interventricular septum and left ventricle but not in the right ventricle. The reduction in tissue noradrenaline concentration was not prevented when the 60-min ischemia was replaced by a 10-min ischemia followed by a 50-min perfusion. No modification in noradrenaline output was observed during a 60-min ischemia. In contrast, reperfusion was accompanied by a washout of noradrenaline in the coronary effluent, corresponding to only 2% of the amount lost by the tissue. The effect of monoamine oxidase inhibition during the whole ischemic period was studied by perfusing the preparation with pargyline starting 10 min before the artery ligation. Although the administration of pargyline did not alter the noradrenaline output, it did prevent a reduction in myocardial noradrenaline concentration. It was concluded that monoamine oxidase may contribute to the elimination of the noradrenaline lost by the cardiac tissue during ischemia.

Animals↗
PubMed1990

Beneficial effect of perindopril, an angiotensin-converting enzyme inhibitor, on left ventricular performance and noradrenaline myocardial content during cardiac failure development in the rat.

The left coronary artery in rats was ligated for a period of 15 days to induce hypertrophy of the non-infarcted myocardium. Left ventricular performances were evaluated in the working heart model. In addition, cardiac hypertrophic indices and noradrenaline content were measured. Variables were determined in the absence or presence of the angiotensin-converting enzyme inhibitor, perindopril. A 35 and 60% decrease in the coronary and cardiac output, respectively, and a 57% decrease in the noradrenaline content of the non-infarcted left ventricular free wall were seen. Furthermore, a 15% increase in the heart/body weight ratio was observed in the infarcted group. After chronic treatment of the animals with perindopril (2 mg.kg-1 body weight, per os), coronary and cardiac output were impaired to a lesser extent: 8 and 35% respectively, with only a 15% decrease in the noradrenaline content of the non-infarcted left ventricular free wall. Furthermore, the increase in heart/body weight ratio was significantly less than in the nontreated infarct group (7%). We conclude that the beneficial effects of converting enzyme inhibition, during the development of myocardial infarction, on left ventricular performances are associated with a decrease in the hypertrophic indices and a normalization of sympathetic activity.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Converting enzyme inhibitors (captopril, enalapril, perindopril) prevent early-post infarction ventricular fibrillation in the anaesthetized rat.

The angiotensin-converting enzyme inhibitors, captopril, enalapril and perindopril, exert antiarrhythmic effects on early post-infarction arrhythmias in anaesthetized rats. These studies support the hypothesis that converting enzyme inhibitors could have a "cardioprotective" effect, but the doses used are probably "high" in relation to those therapeutically applicable to man.

Anesthesia↗
PubMed1987

Protective effect of angiotensin converting enzyme inhibitors (CEI): captopril and perindopril on vulnerability to ventricular fibrillation during myocardial ischemia and reperfusion in rat.

The purpose of the present study was to evaluate the effects of two CEI: captopril and perindopril on reperfusion arrhythmias and noradrenaline 3H (NA3H) release in the isolated rat heart on arrhythmias in pentobarbitone anaesthetized rats subject to left coronary artery ligation. In vitro, in control preparations, reperfusion after 10 min of local ischemia produced by coronary ligation was accompanied by a sudden release of NA3H in coronary flow and long lasting ventricular arrhythmias. Reperfusion arrhythmias were prevented by perfusion medium containing a high dose of CEI and CEI did not change the patterns of NA3H release. In vivo, mortality due to ventricular fibrillation was significantly reduced in rats pretreated with captopril or perindopril 15 min prior to coronary ligation. CEI reduced the severity of ventricular tachycardia (VT) and fibrillation (VF).

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Hypertension in transgenic (mREN2)27 rats is not associated with the presence of B1 receptors.

B1 receptors are inducible receptors expressed only in stressful conditions. The aim of this study was to determine if, in (mREN2)27 transgenic rats, hypertension is associated with the presence of B1 receptors in the cardiovascular system and if a heat stress inducible effect is preserved during hypertension. Age-matched (16 weeks old) heterozygous hypertensive transgenic (mREN2)27 rats (HT rats) and the normotensive control animals (homozygous Sprague-Dawley rats, NT rats) were used. The study was conducted in two parts: in the first part the responsiveness of B1 receptors was studied in rats submitted to heat stress (42 degrees C rectal temperature, 20 min) or sham anaesthesia 24 h before, by recording changes in isometric tension in aortic rings in response to [des-Arg9]-bradykinin, a B1 receptor agonist. In the second part, we studied whether B1 receptor mRNA was present in aorta, heart and kidneys, using a semi-quantitative RT-PCR technique. [des-Arg9]-Bradykinin induced a concentration-dependent relaxation of aortic rings only from animals submitted to prior heat stress. This response was significantly higher in aortic rings from heat stressed HT rats than from heat stressed NT ones. B1 receptor mRNA was undetectable in organs from rats not submitted to heat stress but they were present 5 h after heat stress in aorta, heart and kidneys from both NT and HT rats. In conclusion, arterial hypertension observed in (mREN2)27 rats is not associated with the presence of B1 receptors. However, after heat stress, we observed an increase in responsiveness from HT rat aortas compared to NT ones.

Acetylcholine↗