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-alphaCGRP)-induced responses and the reproducibility of rat-alphaCGRP concentration-response curves were investigated in the left intramural coronary artery of Sprague-Dawley rats. Rat-alphaCGRP (10(-11)-10(-7) M) induced concentration-dependent relaxations with a pD2-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-alphaCGRP were significantly and inversely correlated with vessel lumen diameter. The coronary arteries developed tachyphylaxis in response to rat-alphaCGRP, which was concentration dependently decreased by activating the vessels twice with a buffer containing 36 or 125 mM K+. The rat-alphaCGRP-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-alphaCGRP in intramural rat coronary arteries because the arteries become more sensitive and reactive to rat-alphaCGRP with decreasing caliber. Tachyphylaxis can be avoided by repeated activation with 125 mM K+.
Department of Pharmacology, The Royal Danish School of Pharmacy, Copenhagen O. mash@mail.dfh.dk
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Sheykhzade
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Nyborg
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D003331:Coronary Vessels / Q000033:anatomy & histology / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D008297:Male; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012701:Serotonin / Q000494:pharmacology; D013618:Tachyphylaxis; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*
D012701:Serotonin; D015740:Calcitonin Gene-Related Peptide; D011188:Potassium