Aim: 

The present work was designed to examine the participation of Ca²⁺-activated K⁺ channels on neurogenic-induced contractions in human saphenous veins as well as the intervention of dihydropyridine-sensitive Ca²⁺ channels on modulation of adrenergic responses by K⁺ channels blockade.

Methods: 

Saphenous vein rings were obtained from 40 patients undergoing coronary artery bypass surgery. The vein rings were suspended in organ bath chambers for isometric recording of tension. Electrical field stimulation (EFS, 1, 2, 4 Hz, 15 V, 0.25 ms duration for 15 s) was provided by a Grass S88 stimulator via two platinum electrodes positioned on each side and parallel to the axis of the vascular ring.

Results: 

EFS induced frequency-dependent increases in tension in all the experiments that were abolished by tetrodotoxin (10^-6 M) and prazosin (10^-6 M), thus indicating that the effect was due to the release of NE from perivascular adrenergic nerves acting on a₁-adrenoceptors. Iberiotoxin (10^-7 M), an inhibitor of large-conductance Ca²⁺-activated K⁺ channels, and charybdotoxin (10^-7 M), an inhibitor of both large- and intermediate-conductance Ca²⁺-activated K⁺ channels, enhanced the contractions elicited by electrical field stimulation. In contrast, the inhibitor of small-conductance Ca²⁺-activated K⁺ channels apamin (10^-6 M) did not modify the contractile response to electrical field stimulation. In the presence of the dihydropyridine Ca²⁺-channel blocker nifedipine (10^-6 M), iberiotoxin and charybdotoxin failed to enhance the contractile responses to electrical field stimulation.

Conclusion: 

The present study demonstrates that neurally released noradrenaline activates large-conductance Ca²⁺-activated K⁺-channels in human saphenous vein. This effect may limit venous smooth muscle contraction in response to adrenergic stimulation. Inhibition of these channels increases significantly the contraction, an effect which appears to be mediated by an increase in Ca²⁺ entry through L-type voltage-dependent Ca²⁺ channels.

This work was supported by Conselleria de Educacion, Generalitat Valenciana