Rescue treatment with a Rho-kinase inhibitor normalizes right ventricular function and reverses remodeling in juvenile rats with chronic pulmonary hypertension.
The correlation of changes in PVR and plasma ET-1 levels in responders suggests that high plasma ET-1 is a key mediator of poor response in PH secondary to MS, after iNO therapy.
Upregulated neurohumoral factors are associated with left ventricular remodeling and poor prognosis in rats with monocrotaline-induced pulmonary arterial hypertension.
We have tested the hypothesis that the 5HTT gene does contribute to the pathogenesis of this disease in children by comparing the allelic frequencies of both the long and short variants between children with idiopathic pulmonary hypertension and pulmonary hypertension secondary to underlying pulmonary disease.
In patients carrying the LL genotype, which is associated with higher levels of 5-HTT expression in pulmonary artery smooth muscle cells than the LS and SS genotypes, PH was more severe than in LS or SS patients.
Finally, we suggest that these observations may help to explain why patients with pulmonary hypertension experience exacerbations after taking indomethacin and that the newly introduced selective cyclooxygenase-2 inhibitors may increase endothelin-1 production in susceptible patients, leading to vascular remodeling and the development of pulmonary hypertension.
These data show that, in rats, the increased 5-HTT expression that follows dexfenfluramine discontinuation promotes the development of hypoxic pulmonary hypertension.
These results indicate that chronic fenfluramine exposure potentiates the pulmonary vasoconstrictor response to ET-1, and suggests that elevated levels of serotonin may <prime> the pulmonary circulation to become hyperreactive to other vasoactive substances possibly leading to the development of disease states such as primary pulmonary hypertension.
To explain the increase in potency it is speculated that during the development of pulmonary hypertension the mechanism whereby ET-1 and NA contract pulmonary arteries may change from one in which Ca2+ influx plays only a minor role to one in which Ca2+ influx predominates, although no direct evidence to support this speculation has yet been obtained.
Molecular and functional analysis identifies ALK-1 as the predominant cause of pulmonary hypertension related to hereditary haemorrhagic telangiectasia.