Caliber dependent calcitonin gene-related peptide-induced relaxation in rat coronary arteries: effect of K + on the tachyphylaxis

The influence of vessel caliber on rat calcitonin gene-related peptide (rat- αCGRP)-induced responses and the reproducibility of rat- αCGRP concentration–response curves were investigated in the left intramural coronary artery of Sprague–Dawley rats. Rat- αCGRP (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 to rat- αCGRP were significantly and inversely correlated with vessel lumen diameter. The coronary arteries developed tachyphylaxis in response to rat- αCGRP, which was concentration dependently decreased by activating the vessels twice with a buffer containing 36 or 125 mM K +. The rat- αCGRP-curve became fully reproducible after activation of the arteries twice with 125 mM K +. These results indicate a caliber-related dependency of both the effect of and sensitivity to rat- αCGRP in intramural rat coronary arteries because the arteries become more sensitive and reactive to rat- αCGRP with decreasing caliber. Tachyphylaxis can be avoided by repeated activation with 125 mM K +.