Characterization of vasoconstrictor-induced relaxation in the cerebral basilar artery

The vascular endothelium regulates vascular smooth muscle functions by releasing endothelium-derived vasoactive substances. To identify physiological mechanisms mediating the inhibitory effect of the endothelium on vasoconstrictors, the basilar arteries isolated from Wistar rats were used in an organ bath study. In the intact basilar artery (with endothelium), 100 nM serotonin (5-HT) induced phasic contraction (28.7 ± 4.1% of 60 mM KCl-induced contraction) followed by profound time-dependent relaxation at 3 min (3.8 ± 0.4%). In the denuded artery (without endothelium), the 5-HT-induced contraction was enhanced (51.7 ± 16.1%), while the relaxation was abolished. In the intact basilar artery, the contraction was facilitated and the amplitude of the phasic contraction was significantly enhanced (70.1 ± 10.3%), but time-dependent relaxation was still manifested at 3 min (25.7 ± 10.0%) in the presence of Nω-nitro-l-arginine methyl ester hydrochloride (L-NAME) and indomethacin. Time-dependent relaxation induced by 5-HT was abolished in Ca2+-free and in K+-free Krebs–Henseleit buffer (KHB). Furthermore, the 5-HT-induced contraction was enhanced by treatment with ouabain (105.6 ± 11.8%), tetraethylammonium chloride (133.2 ± 7.9%), charybdotoxin with apamin (145.4 ± 6.4%) or BaCl2 (72.2 ± 13.8%) at 3 min; also, time-dependent relaxation was abolished by these blockers in the presence of L-NAME and indomethacin. U46619 (100 nM) induced sustained contraction without time-dependent relaxation in normal KHB, but charybdotoxin with apamin did not affect the contraction. The results suggest that time-dependent relaxation is modulated by endothelial sodium-potassium pump (Na+/K+-ATPase) and Ca2+-activated K+ channel (KCa) activity, especially small- and intermediate-conductance KCa-prominent ionic mechanisms of the so-called endothelium-derived hyperpolarizing factor.