Endogenous nitric oxide modulates adrenergic neural vasoconstriction in guinea-pig pulmonary artery.

1 Electrical field stimulation (EFS) of guinea-pig isolated pulmonary artery induced a frequency-dependent contraction. This was abolished by tetrodotoxin (1 μm) and prevented by phentolamine and prazosin (both 1 μm), indicating a role for α1-adrenoceptors activated by noradrenaline (NA) released from perivascular adrenergic nerves. 2 l-NG-monomethyl arginine (l-NMMA, 0.3–100 μm) caused a concentration-dependent enhancement of the EFS-induced contraction with a 3.4 ± 0.5 fold increase at 100 μm (n = 6). The augmenting effect of 30 μm l-NMMA on the contraction to EFS was completely reversed by 100–300 μm l-arginine, but not by an identical concentration of d-arginine. 3 The contractile response to exogenous NA was similarly enhanced by 30 μm l-NMMA (2.9 ± 0.6 fold increase, n = 5). 4 The contractile responses to exogenous phenylephrine and prostaglandin F2α which matched the contraction to EFS (4 Hz) were equally augmented by 30 μm l-NMMA. 5 In vessel rings submaximally contracted with the thromboxane analogue U44069 (2 μm), the selective α2-adrenoceptor agonist UK14304 induced concentration-dependent relaxation, which was abolished by removal of endothelium. NA had little relaxant effect on these precontracted vessel rings unless in the presence of prazosin (1 μm). 6 Indomethacin had no significant effect on the contractile response to EFS or NA, indicating that vasodilator cyclo-oxygenase products such as prostacyclin are not involved in modulating these responses. 7 Our results suggest that endogenous nitric oxide inhibits the contractile response to adrenergic nerve stimulation in the guinea-pig pulmonary artery by a postjunctional mechanism, but release of prostacyclin does not modulate these responses. Basal release of nitric oxide from endothelial cells may account for this inhibition.