Electrical field stimulation-induced excitatory responses of pulmonary artery rings from monocrotaline-induced pulmonary hypertensive rats: influence of the endothelium

Abstract

Background: Nitric oxide-mediated endothelium-dependent relaxation is attenuated in pulmonary artery segments from monocrotaline (MCT)-induced pulmonary hypertensive rats. However, the influence of the endothelium on adrenergic neurotransmission in the rat pulmonary artery has not been investigated. The aim of the present study was to investigate the effect of the endothelium on electrical field stimulation (EFS)-induced excitatory responses of pulmonary artery segments from pulmonary hypertensive rats.
Methods: Pulmonary hypertension was induced in rats with a single dose of monocrotaline (60 mg/kg) and 21 days later, arterial rings were set up for isometric tension recording. EFS-induced contractions were recorded in the presence or absence of drugs.
Results: Electrical field stimulation (EFS) induced frequency-dependent contractions in artery segments from control rats and these contractions were not affected by removing the endothelium. L-NAME (10-4 M), a nonselective NO synthase inhibitor, but not 7-NI, a selective neuronal NO synthase inhibitor, potentiated EFS-induced contractions. In addition, L-NAME had no effect on EFS-induced contractions in artery segments without the endothelium indicating a role for endotheliumderived NO in modulating adrenergic neurotransmission in the pulmonary artery. EFS also induced frequency-dependent contractions of artery segments from pulmonary hypertensive rats. These contractions, expressed relative to KCl-induced contractions, were greater in artery segments from pulmonary hypertensive rats. L-NAME (10-4 M) potentiated EFS-induced contractions of artery segments from MCT-treated rats and did not discriminate between artery segments from control and MCT-treated rats. L-NAME potentiated noradrenaline-induced contractions in artery segments from both groups indicating that the effect of L-NAME was mediated post-junctionally.
Conclusion: Monocrotaline-induced pulmonary hypertension is associated with enhanced contractile response to EFS In addition, the modulatory effect of endothelial nitric oxide is unaltered in artery segments from pulmonary hypertensive rats.

Keywords: Monocrotaline, pulmonary artery, pulmonary hypertension, electrical field stimulaion, NO synthase