Cardiologie – Tout Savoir Sur Le Métier De Cardiologue – Doctissimo
Despite these drawbacks, however, angiogenesis remains a very tempting and innovative target in portal hypertension therapy, and researchers are exploring new agents and approaches to maximize the beneficial effects of anti-angiogenic therapies in cirrhosis. Of note, in our experimental studies we have used doses of anti-angiogenic agents over one order of magnitude lower than those used clinically for cancer, which had no noticeable adverse effects in mice or rats. These may be partly overcome by using anti-angiogenic agents that do not interfere with physiological angiogenesis since they act predominantly on pathological angiogenesis. It is now clear that vasoactive mediators, either vasoconstrictors or vasodilators, may modulate intra-hepatic vascular resistance either in health or during liver disease, whatever the location where they act. HMG-CoA reductase inhibitor increases GTP cyclohydrolase I mRNA and tetrahydrobiopterin in vascular endothelial cells.Arterioscler Thromb Vasc Biol.
These findings indicate that angiogenesis is involved in the development of the portosystemic collateral and in the maintenance of an increased portal venous inflow, and strongly support that agents interfering with the VEGF/VEGFR-2 signalling pathway may potentially be used to prevent these complications of portal hypertension. All these findings suggest that in cirrhotic livers there is an over-activation of the COX-1 pathway with an increased production of their vasoconstrictor-derived compounds, and that correcting these abnormalities will have beneficial effects on hepatic circulation. Beneficial effects of sorafenib on splanchnic, intrahepatic, and portocollateral circulations in portal hypertensive and cirrhotic rats.Hepatology.
Hypertension Symptomes Yeux
In these conditions, the beneficial effect of acute ascorbic acid administration has been attributed to its capacity of neutralizing ROS, mainly superoxide (O2-). This further demonstrates that in chronic liver disease, reduced intra-hepatic NO bioavailability is due not only to the consequence of a reduction in its production by eNOS synthase, but also to an increase in scavenging by increased levels of superoxide. Thus, an increased production of superoxide and a diminished degradation are the causes of the increased superoxide levels observed in the cirrhotic livers. We have recently shown that increased O2- levels in the cirrhotic liver is associated with reduced superoxide dismuatse (SOD) activity, the enzyme dismutating O2- to H2O2, suggesting that this maybe its mechanism. Superoxide dismutase gene transfer reduces portal pressure in CCl4 cirrhotic rats with portal hypertension.Gut. The eNOS cofactor tetrahydrobiopterin improves endothelial dysfunction in livers of rats with CCl4 cirrhosis.Hepatology.
The first attempt was the exogenous administration of NO donors.
Statins increase eNOS expression and activity. BH4, secondary to a reduction in the expression and activity of Guanosine-5’-triphosphate cyclohydrolase I (GTPCHI), the limiting enzyme in BH4 synthesis, which is associated with decreased NOS activity and NO availability. Fig. 5).Fig. 5Transfection with adenovirus encoding EC-SOD improves the endothelial dependent vasorelaxation in perfused cirrhotic livers (upper panel) and decreases portal pressure in vivo in cirrhotic rats (lower panel). Pression artérielle nice . Of note, a study from our group has shown that cirrhotic patients had significantly lower ascorbic acid levels and higher malondialdehyde levels (MDA: a serum marker of oxidative stress) than healthy controls. Increased oxidative stress in cirrhotic rat livers: a potential mechanism contributing to reduced nitric oxide bioavailability.Hepatology. These results suggest that in portal hypertension, increased shear stress, related to high blood flow, induces enhanced aortic NOS3. These data support the concept that tetrahydrobiopterin supplementation may represent a new and effective therapeutic strategy for portal hypertension. Supplementation with exogenous BH4 decreases portal pressure in cirrhotic rats. The first attempt was the exogenous administration of NO donors. In normal conditions, the endothelium is able to generate vasodilatory factors in response to increases in blood volume, blood pressure, or vasoconstrictor agents, in an attempt to prevent or attenuate the concomitant increase in intravascular pressure.
Hypertension Diastolique Traitement Naturel
Enhanced vasoconstrictor prostanoid production by sinusoidal endothelial cells increases portal perfusion pressure in cirrhotic rat livers.J Hepatol. The relationship between NO bioavailability and O2- content in the liver is further supported by our experiments in sinusoidal endothelial cells (SEC) demonstrating that NO bioavailability is modulated by O2-. Possible involvement of endothelin 1 and nitric oxide in the regulation of the sinusoidal tonus.Eur J Biochem. Rosuvastatin, a new HMG-CoA reductase inhibitor, upregulates endothelial nitric oxide synthase and protects from ischemic stroke in mice.Brain Res. Sustained increase in aortic endothelial nitric oxide synthase expression in vivo in a model of chronic high blood flow. Omega 3 et hypertension . Aortic expression of RhoA was unchanged in cirrhotic rats, whereas Rho-kinase was down-regulated posttranscriptionally. Abnormal regulation of aortic NOS2 and NOS3 activity and expression from portal vein-stenosed rats after lipopolysaccharide administration. Upon ligand binding to VEGFR-2, PI3K is also activated leading to activation of the protein kinase Akt, which in turn phosphorylates eNOS and increases NO production. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals.Nat Med.
Methoxamine-induced activation of RhoA as well as basal and methoxamine-induced phosphorylation of moesin were strongly reduced in aortas from cirrhotic rats. The left femoral artery and vein were cannulated with PE-50 catheters for measurement of arterial pressure and blood withdrawal as well as for drug infusion. Thereafter, MAP was measured in 5-minute intervals for another 45 minutes, followed by measurement of the cardiac output. The catheter in the femoral artery was connected to a pressure transducer (Hugo Sachs Elektronik, March-Hugstetten, Germany) for blood pressure measurement. To revert established new blood vessels, multi-target agents or a combination of agents blocking both VEGF and PDGF is required. Nitric oxide as a mediator of hemodynamic abnormalities and sodium and water retention in cirrhosis. Simvastatin enhances hepatic nitric oxide production and decreases the hepatic vascular tone in patients with cirrhosis.Gastroenterology. Oxidative stress and vascular disease: 2005 Duff lecture.Arterioscler Thromb Vasc Biol. Efficacy and safety of high-dose pravastatin in hypercholesterolemic patients with well-compensated chronic liver disease: results of a prospective, randomized, double-blind, placebo-controlled, multicenter trial.Hepatology. Total aortic NOS activity was higher in portal vein-stenosed aortas and significantly decreased after β-blocker administration. Conclusions: In portal hypertension, aortic NOS3 activity and expressions are enhanced but return to normal after β-blocker administration.