Influences of the endothelium and hypoxia on neurogenic transmission in the isolated pulmonary artery of the rabbit.

1. The effects of nitric oxide (10(-6) M), N omega-nitro-L-arginine methylester (L-NAME, 10(-4) M, an inhibitor of nitric oxide synthase), endothelium removal, hypoxia and selective alpha-adrenoceptor antagonists on responses to nerve electrical field-stimulation (EFS) were studied in the rabbit isolated pulmonary artery. 2. EFS induced frequency-dependent contractions which were abolished by prazosin (alpha 1-adrenoceptor antagonist) and unaffected by rauwolscine (alpha 2-adrenoceptor antagonist). EFS-induced responses were potentiated by L-NAME and inhibited by nitric oxide. The effect of L-NAME was reversed by the presence of L-arginine (2 x 10(-4) M), which had no effect on its own. In the presence of L-NAME, the EFS-induced responses were reduced by rauwolscine and the residual responses were abolished by prazosin. 3. Removal of the vascular endothelium increased the maximum contractile response to EFS but did not inhibit the ability of L-NAME to potentiate contractile responses to EFS. 4. Hypoxia inhibited the contractile response to EFS. This effect of hypoxia was also seen in the presence of L-NAME and in endothelium rubbed preparations. 5. In conclusion, the endothelium modulates EFS-induced contractions in the rabbit pulmonary artery. The contraction induced by EFS was inhibited by nitric oxide, but potentiated by the nitric oxide-synthase inhibitor, L-NAME. The effect of L-NAME was not mediated solely through the endothelium and revealed involvement of alpha 2-adrenoceptors in EFS-induced contraction. Hypoxia inhibited neurogenic responses in rabbit isolated pulmonary arteries.