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At least 37 records · Page 2Linked to original sources
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↗
PubMed1981

Effect of alpha naphthylthiourea on uptake of 5-hydroxytryptamine from the pulmonary circulation.

Pulmonary injury caused by alpha naphthylthiourea (ANTU) is characterized by alterations of the capillary endothelial barrier followed by lung edema. Because pulmonary uptake of 5-hydroxytryptamine (5-HT) is dependent upon active transcellular transport by lung endothelium, it may be an index of early impairment of endothelial function caused by ANTU. We studied the effect of a single intraperitoneal dose of 5 or of 10 mg/kg of ANTU on pulmonary uptake of 5-HT by isolated rat lungs. Four h after the administration of ANTU, when lung tissue structure and dry-to-wet-weight ratios were comparable to those of control animals, 5-HT uptakes were significantly reduced (p < 0.05). Twenty-four h after the administration of ANTU, when lung edema was present on histologic examination and by lung weights, 5-HT uptakes were further reduced. They returned to control values 14 days after the administration of ANTU. Depression of 5-HT uptake is an early and reversible alteration of lung endothelial cell function caused by ANTU. Uptake of 5-HT may provide a sensitive probe with which to detect and evaluate pulmonary endothelial cell injury caused by toxicants.

Animals↗
PubMed2005

Effects of dobutamine on right ventricular function and pulmonary circulation in pulmonary hypertension during liver transplantation.

INTRODUCTION: In the setting of orthotopic liver transplantation (OLT), pulmonary hypertension (PH) affects right ventricular (RV) function. When RV failure occurs, reducing RV afterload, optimizing RV preload, and preserving coronary perfusion through maintenance of systemic blood pressure are the primary goals of intraoperative treatment. PATIENTS AND METHODS: To verify the effect of dobutamine on RV function and RV-arterial coupling, we compared a group of 9 cirrhotic patients with mild PH treated with OLT to a group of 20 patients with normal mean pulmonary artery pressure (MPAP). All patients received dobutamine (5-10 microg/kg/min) to maintain a cardiac index (CI) >3 L/min/m(2), during the anhepatic phase. Hemodynamic profile, using a pulmonary artery catheter, was performed before and during dobutamine infusion, studying MPAP, CI, and RV end-diastolic volume index (RVEDVI). RV stroke work index (RVSWI), RV end-systolic elastance (Ees), pulmonary effective elastance (Ea), and RV-arterial coupling efficiency as the Ees/Ea ratio were also calculated. RESULTS: RV contractility (Ees and RVSWI) and afterload (Ea) were significantly higher among the PH group. In both groups, all the studied variables improved with dobutamine: RV contractility increased, afterload decreased, and thus Ees/Ea coupling markedly increased. CONCLUSION: Cirrhotic patients with mild PH who were undergoing OLT still have a reserve of RV contractile performance and pulmonary vasodilation.

Cardiotonic Agents↗