Vascular reactivity in pulmonary resistance arteries : influence of pulmonary hypertension and endothelin
The main aim of my research was to investigate the vascular reactivity of pulmonary resistance arteries in vitro, and assess any functional changes which may occur as a result of pulmonary hypertension. Particular influence was given to investigation of the vascular effects ET-1 in pulmonary arteries, and characterisation of the ET receptors present in these vessels. To investigate changes in vascular reactivity in pulmonary hypertension, a chronic hypoxic rat model was utilised. In control adult rats, ET-1 (non selective ETA/ETB receptor agonist) produced potent vasoconstrictor responses in both large extrapulmonary arteries (3-5 mm i.d.) and pulmonary resistance arteries (?150 m i.d.) whereas responses to SxS6c (selective ETB agonist) were observed only in pulmonary resistance arteries. The selective ETA receptor antagonist FR 139317 was more effective in attenuating ET-1 mediated vasoconstriction in larger calibre pulmonary arteries than in pulmonary resistance arteries. Therefore it was found that ETA receptors predominate in large calibre extrapulmonary arteries, but pulmonary resistance arteries contain populations of both ETA and ETB receptors mediating vasoconstriction. Young male rats exposed to 14-16 days chronic hypobaric (418 mmHg) hypoxia exhibited significantly increased pulmonary artery pressure, right ventricular hypertrophy and pulmonary vascular remodelling all of which are associated with the development of pulmonary hypertension. Responses to ET-1 were significantly augmented in chronic hypoxic rat pulmonary resistance arteries compared to age matched controls, and this potentiation appeared to be mediated via activation of ETA receptors.