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Abstract. Radial artery (RA) is increasingly used as graft for coronary artery bypass grafting due to its good long-term patency. However, the mechanism of peri-and post-operative spasm is still unclear. Because of that, the aim of our study is to analyze the contractility of RA and to determine whether the presence of functional endothelium alters its contractile properties. Contractions of isolated RA rings were provoked by exogenously applied vasoconstrictors or by electrical field stimulation (EFS, 20 Hz). The order of vasoconstrictors potency based on their EC 50 values was as follows: angiotensin II > phenylephrine > 5-hydroxytriptamine. Presence of endothelium increased both EC 50 and maximal contraction to phenylephrine and angiotensin II, but inhibited reactivity of RA to 5-hydroxytriptamine. Spontaneous rhythmic contractions (SRC, <4 mHz) and EFS-induced contractions of RA are endothelium-independent and weaker than contractions induced by exogenously applied vasoconstrictors. Our study concludes that RA shows marked sensitivity and reactivity to angiotensin II, phenylephrine, and 5-hydroxytriptamine. Further investigations are necessary to answer why angiotensin II and phenylepehrine induce stronger contractions in the presence of endothelium. In addition, SRC as well as contractions of neurogenic origin may take part in developing vascular spasm of RA.

Abstract. Taking into consideration that the search for drugs capable of modifying blood flow through human radial artery (RA) is warranted, the present study was designed to examine the vasodilatatory effects of the potassium channel opener, pinacidil on the RA and to define the contribution of different K + -channel subtypes in the endothelium-independent pinacidil action on this blood vessel. Pinacidil relaxed the RA rings with endothelium and without endothelium with comparable potency. N-nitro-L-arginine methyl ester (L-NAME) and methylene blue did not affect the pinacidil-induced vasorelaxation in rings with endothelium. In the rings without endothelium, the K + -channel blockers glibenclamide and tetraethylammonium (TEA) moderately antagonized the pinacidil-induced relaxation, while charybdotoxin and 4-aminopiridine did not. In endothelium-denuded rings, precontracted with 100 mM K + , the relaxant responses to pinacidil were highly significantly shifted to the right compared to those obtained in RA precontracted with phenylephrine, but pinacidil-induced maximal relaxation was not affected. Addition of nifedipine did not but addition of nifedipine and nickel (Na + -Ca 2+ exchanger inhibitor) did cause a statistically significant rightward shift of the pinacidil concentration-relaxation curve, although the effect 0.1 mM pinacidil was preserved. Thus, pinacidil induces relaxation of the human RA in endothelium-independent manner, and glibenclamide-and TEA-sensitive vascular smooth muscle K + channels are probably involved. Its ability to completely relax the RA precontracted with K + -rich solution suggests that pinacidil has additional K + channel-independent mechanism(s) of action. It seems that stimulation of the forward mode of the Na + -Ca 2+ exchanger plays a part in this K + channel-independent effect of pinacidil.

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Pinacidil, a prevously studied potassium channel opener (PCO), is a potent antihypertensive agent in animals and humans. Its mechanism of action is not completly defined. The aim of our study was to investigate the antivasoconstricting effect of pinacidil on the isolated RA and to study whether this effect is endothelium-dependent. Contractions of isolated RA rings with intact endothelium were provoked by electrical field stimulation (EFS, 20 Hz) or exogenously applied noradrenaline (NA, 10 μM). Pinacidil (10 nM-0.1 mM) produced a concentration-dependent inhibition of both EFS- and NA-evoked contractions (p>0.05). NO synthesis inhibitor, L-NAME (10 μM) and the guanylate cyclase inhibitor, methylene blue (10 μM) did partly antagonize NA-evoked contractions and were without effect on EFSinduced contractions. Thus, the antivasoconstrictor effect of pinacidil on RA is partly endothelium-dependent and probably mediated via cGMP-dependent NO-pathway