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Jean-Marc Hyvelin

Publications and source records attributed to Jean-Marc Hyvelin.

9 recordsLinked to original sources
PubMed2006

Dexfenfluramine does not worsen but moderates progression of chronic hypoxia-induced pulmonary hypertension.

This study shows for the first time, that dexfenfluramine, a 5-HT(2) receptor agonist, attenuates the development of chronic hypoxia-induced pulmonary hypertension. Chronic exposure to hypoxia, 4 weeks, induced hypoxic pulmonary hypertension in adult rat as haemodynamic and cardiac measurements showed significant modifications in right ventricle parameters (free wall right ventricle thickness; pulmonary acceleration time and velocity time integral) in chronic hypoxic control when compared to normoxic control animals. We observed that free wall right ventricle thickness and pulmonary velocity time integral were significantly less in chronic hypoxic rats treated with dexfenfluramine when compared to chronic hypoxic control rats. Similarly, rats exposed to chronic hypoxia exhibited an increase in both right ventricle pressure and weight by comparison to normoxic control animals but those variations were significantly diminished in dexfenfluramine-treated rats, indicating the moderating influence exerted by dexfenfluramine on chronic hypoxia-induced pulmonary hypertension and cardiac alterations. Thus, we report here the ability of dexfenfluramine to limit chronic hypoxia-induced pulmonary hypertension, emphasizing the importance of the time after the dexfenfluramine treatment discontinuation to assess the influence of this 5-HT receptor agonist on the development of chronic hypoxia-induced pulmonary hypertension.

Animals↗
PubMed2006

Heterogeneous Kv1 function and expression in coronary myocytes from right and left ventricles in rats.

Coronary blood flow control is not uniform along the vascular tree and particularly between the right coronary artery and the left anterior descending artery. Resting membrane potential that contributes largely to the vascular tone is mainly regulated by K(+) channels in coronary myocytes. In the present study, we hypothesized that right coronary artery (RCA) and left coronary artery (LCA) exhibited a cell-specific function of K(+) channels. The net outward current was markedly greater in RCA compared with LCA cells, and this difference was due to a larger 4-aminopyridine (4-AP)-sensitive voltage-gated potssium (Kv) current in RCA cells, whereas the iberiotoxin (IbTx)-sensitive, large conductance Ca(2+)-dependent potassium (BK(Ca)) current was smaller in RCA cells. To go further in the molecular identity of this Kv current, we used 50 nM correolide, which specifically blocked Kv1 family alpha-subunits. Outward currents generated by ramp depolarization protocols were highly sensitive to correolide in both RCA and LCA cells, suggesting that Kv1 contributed for a large part to the net outward current. 4-AP-induced contractions in isolated RCA, and LCA were greater than IbTx-induced contraction. Furthermore, the 4-AP-induced contraction in RCA was significantly greater than that in LCA, which is in agreement with the electrophysiological data. Finally, the Kv1.2 alpha-subunit but not the Kv1.5 was detected in both RCA and LCA using primary specific antibody in Western blotting and immunofluorescence assay, and expression of Kv1.2 alpha-subunit was markedly higher in RCA compared with LCA. In summary, we reported for the first time a heterogeneous function and expression of Kv1 alpha-subunits in rat coronary myocytes isolated from RCA or LCA.

Animals↗
PubMed2005

Inhibition of Rho-kinase attenuates hypoxia-induced angiogenesis in the pulmonary circulation.

Pulmonary hypertension (PH) is a common complication of chronic hypoxic lung diseases, which increase morbidity and mortality. Hypoxic PH has previously been attributed to structural changes in the pulmonary vasculature including narrowing of the vascular lumen and loss of vessels, which produce a fixed increase in resistance. Using quantitative stereology, we now show that chronic hypoxia caused PH and remodeling of the blood vessel walls in rats but that this remodeling did not lead to structural narrowing of the vascular lumen. Sustained inhibition of the RhoA/Rho-kinase pathway throughout the period of hypoxic exposure attenuated PH and prevented remodeling in intra-acinar vessels without enlarging the structurally determined lumen diameter. In chronically hypoxic lungs, acute Rho kinase inhibition markedly decreased PVR but did not alter the alveolar to arterial oxygen gap. In addition to increased vascular resistance, chronic hypoxia induced Rho kinase-dependent capillary angiogenesis. Thus, hypoxic PH was not caused by fixed structural changes in the vasculature but by sustained vasoconstriction, which was largely Rho kinase dependent. Importantly, this vasoconstriction had no role in ventilation-perfusion matching and optimization of gas exchange. Rho kinase also mediated hypoxia-induced capillary angiogenesis, a previously unrecognized but potentially important adaptive response.

Amides↗
PubMed2005

CO inhalation at dose corresponding to tobacco smoke worsens cardiac remodeling after experimental myocardial infarction in rats.

We hypothesized that inhalation of carbon monoxide (CO) (500 ppm), similar to that in tobacco smoke, disturbs the cardiovascular adaptation after myocardial infarction by increasing remodeling. Four groups of rats were assessed. Two groups had myocardial infarction induced by the ligation of the left coronary artery: the first group was exposed to air (infarcted air group, n = 12), and the second was exposed to CO (infarcted CO group, n = 11). They were compared to two sham-operated groups, a control air group (n = 10), and a control CO group (n = 7) exposed (3 weeks) to CO. Aerobic endurance capacity was assessed in both the infarct CO and infarct air group (endurance capacity = 0.043 +/- 0.006 m.min(-1).g(-1) vs. 0.042 +/- 0.005 m.min(-1).g(-1), not significant). In the infarcted CO group compared to the infarcted air group, the dilatation of the left ventricle observed 3 weeks after infarction was increased, (left ventricular diastolic (LVD) diameter (D) = 9 +/- 0.4 vs. 7 +/- 0.4 mm, p < 0.05; left ventricular systolic (LVS) diameter (D) = 6 +/- 0.6 vs. 4.1 +/- 0.4, p < 0.05), and the diastolic posterior wall thickness was augmented (posterior wall diastolic thickness = 1.7 +/- 0.1 vs. 1.3 +/- 0.1 mm, p < 0.05). Hemodynamic pressure measurements in both ventricles and pulmonary artery showed elevated diastolic pressure after CO exposure compared to air exposure (LVD pressure = 32 +/- 1.6 vs. 19 +/- 2.3 mm Hg, p < 0.05; right ventricular diastolic pressure = 16 +/- 1.6 vs. 8.6 +/- 1.6 mm Hg, p < 0.05; pulmonary arterial pressure in diastole (PAD) = 27 +/- 1.6 vs. 20 +/- 2.3 mm Hg, p < 0.05). In the infarcted CO group, the infarct size increased. Echocardiography and histology showed hypertrophy of the contralateral wall similar to that observed in the noninfarcted control CO group. In conclusion, chronic CO inhalation worsens heart failure in rats with myocardial infarction by an increase in the infarct size and hypertrophy remodeling.

Administration, Inhalation↗
PubMed2004

Effect of changes in pH on wall tension in isolated rat pulmonary artery: role of the RhoA/Rho-kinase pathway.

Pulmonary arteries (PA) are resistant to the vasodilator effects of extracellular acidosis in systemic vessels; the mechanism underlying this difference between systemic and pulmonary circulations has not been elucidated. We hypothesized that RhoA/Rho-kinase-mediated Ca2+ sensitization pathway played a greater role in tension development in pulmonary than in systemic vascular smooth muscle and that this pathway was insensitive to acidosis. In arterial rings contracted with the alpha1-agonist phenylephrine (PE), the Rho-kinase inhibitor Y-27632 (< or =3 microM) induced greater relaxation in precontracted PA rings than in aortic rings. In PA rings stimulated by PE, the activation of RhoA was greater than in aorta. Normocapnic acidosis (NA) induced a smaller relaxation in precontracted PA than in aorta. However, in the presence of nifedipine and thapsigargin, when PE-induced contraction was predominantly mediated by Rho-kinase, the relaxant effect of NA was reduced and similar in both vessel types. Furthermore, in the presence of Y-27632, NA induced a greater relaxation in both PA and aorta, which was similar in both vessels. Finally, in alpha-toxin-permeabilized smooth muscle, PE-induced contraction at constant Ca2+ activity was inhibited by Y-27632 and unaffected by acidosis. These results indicate that Ca2+ sensitization induced by the RhoA/Rho-kinase pathway played a greater role in agonist-induced vascular smooth muscle contraction in PA than in aorta and that tension mediated by this pathway was insensitive to acidosis. The predominant role of the RhoA/Rho-kinase pathway in the pulmonary vasculature may account for the resistance of this circulation to the vasodilator effect of acidosis observed in the systemic circulation.

Amides↗
PubMed2004

Role of cyclooxygenase in ventricular effects of adrenomedullin: is adrenomedullin a double-edged sword in sepsis?

Adrenomedullin (ADM) is upregulated in cardiac tissue under various pathophysiological conditions. However, the direct inotropic effect of ADM on normal and compromised cardiomyocytes is not clear. In rat ventricular myocytes, ADM produced an initial (<30 min) increase in cell shortening and Ca(2+) transient and, on prolonged incubation (>1 h), a marked decrease in cell shortening and Ca(2+) transient. Both effects were sensitive to inhibition by the ADM antagonist ADM-(22-52). The increase and decrease in cell shortening and Ca(2+) transient were attenuated by pretreatment with indomethacin [a nonspecific cyclooxygenase (COX) inhibitor], nimesulide and SC-236 (specific COX-2 inhibitors), and tranylcypromine (a prostacyclin synthase inhibitor); SQ-29548 (a thromboxane receptor antagonist) was without effect. Cells isolated from LPS-treated rats that were in the late, hypodynamic phase of septic shock also showed a marked decrease in cell shortening and Ca(2+) transient. Because ADM is overexpressed in sepsis, we repeated the above protocol in cells isolated from LPS-treated rats. At 4 h after LPS injection, ADM levels markedly increased in plasma, ventricles, and freshly isolated ventricular myocytes. Decreases in cell shortening and Ca(2+) transient in LPS-treated cells were reversed by pretreatment with ADM-(22-52). Anti-ADM (rat) IgG also reversed the decrease in cell shortening and other parameters of cell kinetics. Indomethacin, SC-236, and tranylcypromine restored cell contractility and the decrease in Ca(2+) transient, whereas SQ-29548 had no effect, implying that prostacyclin played a role in both effects. However, with regard to cell-shortening kinetics, indomethacin and SQ-29548 decreased the amount of time taken by the cells to return to baseline, whereas SC-236 and tranylcypromine did not, implying that not only prostacyclin, but also thromboxane, is involved. The results indicate that ADM interacts with COX to yield prostanoids, which mediate its negative inotropic effect in LPS-treated rat ventricular myocytes.

Adrenomedullin↗
PubMed2003

Hypercapnic acidosis attenuates endotoxin-induced acute lung injury.

Deliberate induction of prophylactic hypercapnic acidosis protects against lung injury after in vivo ischemia-reperfusion and ventilation-induced lung injury. However, the efficacy of hypercapnic acidosis in sepsis, the commonest cause of clinical acute respiratory distress syndrome, is not known. We investigated whether hypercapnic acidosis--induced by adding CO2 to inspired gas--would be protective against endotoxin-induced lung injury in an in vivo rat model. Prophylactic institution of hypercapnic acidosis (i.e., induction before endotoxin instillation) attenuated the decrement in arterial oxygenation, improved lung compliance, and attenuated alveolar neutrophil infiltration compared with control conditions. Therapeutic institution of hypercapnic acidosis, that is, induction after endotoxin instillation, attenuated the decrement in oxygenation, improved lung compliance, and reduced alveolar neutrophil infiltration and histologic indices of lung injury. Therapeutic hypercapnic acidosis attenuated the endotoxin-induced increase in the higher oxides of nitrogen and nitrosothiols in the lung tissue and epithelial lining fluid. Lung epithelial lining fluid nitrotyrosine concentrations were increased with hypercapnic acidosis. We conclude that hypercapnic acidosis attenuates acute endotoxin-induced lung injury, and is efficacious both prophylactically and therapeutically. The beneficial actions of hypercapnic acidosis were not mediated by inhibition of peroxynitrite-induced nitration within proteins.

Acidosis, Respiratory↗
PubMedDate not supplied

Adrenomedullin: a cardiac depressant factor in septic shock.

Despite intensive research, septic shock is still the most common cause of death in surgical intensive care, and its incidence keeps increasing. No curative treatment is yet available. The critical aspect of septic shock is the refractory hypotension that develops during its late phase which leads to a progressive deterioration of cell and organ functions, and in most instances, death. During septic shock, following the overproduction of cytokines, many factors such as nitric oxide and adrenomedullin (ADM) are produced in abnormally large quantities, but our understanding of their contribution to the pathophysiology of sepsis is limited. Here we show that adrenomedullin (22-52), an adrenomedullin receptor antagonist, improves the contractility of myocytes isolated from lipopolysaccharide (LPS)-treated rats, whereas in normal myocytes, adrenomedullin, acting through an adrenomedullin (22-52) sensitive receptor, decreases their contractility. In addition, adrenomedullin antiserum and inducible nitric oxide (NO) synthase inhibitor improve the survival of LPS-treated rats. The data indicate that adrenomedullin is a cardiac depressant factor, which along with NO precipitates ventricular failure during septic shock.

Adenylyl Cyclases↗