Comparison of the vasoconstrictor effects of rizatriptan and sumatriptan in human isolated cranial arteries: immunohistological demonstration of the involvement of 5-HT1B-receptors

Aims We compared the vasoconstrictor effects of 5-HT with those of the sele ctive 5-HT1B/1D-receptor agonists sumatriptan and rizatriptan in human isol ated cranial (middle meningeal) arteries. In addition selective 5-HT1B- or 5-HT1D-receptor antibodies were used in combination with semiquantitative i mmunohistochemical techniques to compare the levels of expression of these receptors in human middle meningeal and coronary arteries. Methods Middle meningeal and coronary arteries were obtained (with consent) from either neurosurgical patients or donor hearts, respectively. Segments of middle meningeal artery were mounted in organ baths for isometric recor ding and cumulative concentration-effect curves to 5-HT, rizatriptan and su matriptan were obtained. Frozen fresh sections of middle meningeal and coro nary arteries were subjected to standard immunohistochemical techniques usi ng specific 5-HT1B- or 5-HT1D-receptor primary antibodies and a radiolabell ed secondary antibody. Data were subjected to analysis of variance (ANOVA) and nonlinear regression analysis. Results 5-HT, rizatriptan and sumatriptan were potent vasoconstrictors in h uman isolated middle meningeal artery (EC50 values=32, 90 and 71 nM, respec tively). A significantly higher level of 5-HT1B-receptor immunoreactivity w as detected in middle meningeal artery compared with coronary artery (ANOVA , F=7.95, DF= 1,4, P<0.05). Conclusions Rizatriptan and sumatriptan act selectively to cause vasoconstr iction in human isolated middle meningeal artery and are 10-fold more poten t than in human coronary artery. The higher level of expression of 5-HT1B-r eceptors in middle meningeal compared with coronary artery provides a pharm acological basis for the craniovascular selectively of both rizatriptan and sumatriptan.