CALIBER DEPENDENT CALCITONIN-GENE-RELATED PEPTIDE-INDUCED RELAXATION IN RAT CORONARY-ARTERIES - EFFECT OF K+ ON THE TACHYPHYLAXIS (VOL 351,PG 53, 1998)

xThe influence of vessel caliber on rat calcitonin gene-related peptid e (rat-alpha CGRP)-induced responses and the reproducibility of rat-al pha CGRP concentration-response curves were investigated in the left i ntramural coronary artery of Sprague-Dawley rats. Rat-alpha CGRP (10(- 11)-10(-7) M) induced concentration-dependent relaxations with a pD(2) -value equal to 8.43 +/- 0.05 (n = 44) and maximal relaxation equal to 52 +/- 3% (n = 44). Both the maximal relaxation and the sensitivity o f rat-alpha CGRP were significantly and inversely correlated with vess el lumen diameter. The coronary arteries developed tachyphylaxis in re sponse to rat-alpha CGRP, which was concentration dependently decrease d by activating the vessels twice with a buffer containing 36 or 125 m M K+. The rat-alpha CGRP-curve became fully reproducible after activat ion of the arteries twice with 125 mM K+. These results indicate a cal iber-related dependency of both the effect of and sensitivity to rat-a lpha CGRP in intramural rat coronary arteries because the arteries bec ome more sensitive and reactive to rat-alpha CGRP with decreasing cali ber. Tachyphylaxis can be avoided by repeated activation with 125 mM K +. (C) 1998 Elsevier Science B.V. All rights reserved.