The antivasoconstrictor effect of P1075 on the isolated human saphenous vein

To investigate whether the antivasoconstrictor effect of P1075, a potassium channel openers, could be partly due to modulation of neurotransmitter release from adrenergic nerve endings we analysed the presynaptic and postsynaptic effects of P1075 on the isolated human saphenous vein (HSV). The HSV rings were contracted by electrical field stimulation (EFS) or by exogenous noradrenaline (10 μM; NA). The repetitive transmural EFS was carried out at 20 Hz with square wave pulses of 0.3 ms duration and supramaximal voltage. The contraction of the HSV in response to transmural EFS recorded in our experiments are neurogenic in nature, as this effect was abolished by tetrodotoxin (1 μM). We have also found that phentolamine (1 μM) inhibited almost completly (90 ″ 2%) the HSV contractions to EFS suggesting that this response was mediated by NA release from perivascular sympathetic nerve endings activating postjuncional α adrenoceptors. P1075 (0.01-10 μM) induced a concentration-dependent inhibition of both neurogenic contractions, and contractions evoked by exogenous NA of the HSV with pEC 50 values of of 6.48 ″ 0.05 and 6.36″ 0.08. The difference between the pEC 50 values (r) was not statistically significant (P > 0.05). These results suggest that the antivasoconstrictor effect of P1075 on the HSV might be postsynaptic, and associated with opening of the smooth muscle potassium channels