Electrical field stimulation (EFS) of guinea‐pig isolated pulmonary artery induced a frequency‐dependent contraction. This was abolished by tetrodotoxin (1 μ m ) and prevented by phentolamine and prazosin (both 1 μ m ), indicating a role for α 1 ‐adrenoceptors activated by noradrenaline (NA) released from perivascular adrenergic nerves. l ‐N G ‐monomethyl arginine ( l ‐NMMA, 0.3–100 μ m ) caused a concentration‐dependent enhancement of the EFS‐induced contraction with a 3.4 ± 0.5 fold increase at 100 μ m ( n = 6). The augmenting effect of 30 μ m l ‐NMMA on the contraction to EFS was completely reversed by 100–300 μ m l ‐arginine, but not by an identical concentration of d ‐arginine. The contractile response to exogenous NA was similarly enhanced by 30 μ m l ‐NMMA (2.9 ± 0.6 fold increase, n = 5). The contractile responses to exogenous phenylephrine and prostaglandin F 2α which matched the contraction to EFS (4 Hz) were equally augmented by 30 μ m l ‐NMMA. In vessel rings submaximally contracted with the thromboxane analogue U44069 (2 μ m ), the selective α 2 ‐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 μ m ). 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. 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.
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