Potassium channels sensitive to combination of charybdotoxin and apamin regulate the tone of diabetic isolated canine coronary arteries.
OBJECTIVE
Functional roles of calcium-activated potassium channels on the mechanical activity of epicardial coronary arteries obtained from a canine model of diabetes were investigated.


METHODS
Coronary arteries were isolated from healthy, alloxan-diabetic and insulin-treated diabetic dogs. Basal tensions, contractions induced by the prostaglandin (PG) analogue, U46619, and endothelium-dependent relaxations to acetylcholine (ACh) were modified with charybdotoxin (CHTX) + apamin (APA), inhibitors of calcium-activated potassium channels, as well as with N(omega)-nitro-l-arginine (LNA) + indomethacin (INDO) to suppress the synthesis of nitric oxide (NO) and PGs. The relaxing effect of nitroprusside-sodium (SNP), an NO donor, was also determined.


RESULTS
In diabetic coronary arteries, CHTX + APA did not change while LNA + INDO elevated the basal tension. PG-induced contractions were enhanced by CHTX + APA and by LNA + INDO in all the three groups of animals. CHTX + APA decreased the maximal relaxations to ACh in a partly insulin-dependent manner. LNA + INDO abolished the endothelium-dependent relaxations to ACh. In diabetic coronary arteries, the sensitivity to SNP-induced relaxation was enhanced, insulin independently, suggesting that NO could be partly responsible for maintaining intact ACh-induced vasorelaxation.


CONCLUSIONS
In diabetic canine coronary artery, the vasomotor responses reflect up-regulation of calcium-activated potassium channels. This endothelial mechanism of the canine epicardial coronary artery may oppose vasoconstrictions in diabetic vascular tissue.
Pataricza
J
J
Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary. pataricza@phcol.szote.u-szeged.hu
Márton
Z
Z
Lengyel
Cs
C
Tóth
M
M
Papp
J Gy
JG
Varró
A
A
Kun
A
A
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology*; D018999:Charybdotoxin / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology*; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D007328:Insulin; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D018999:Charybdotoxin; D001030:Apamin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D026423:S-Nitroso-N-Acetylpenicillamine; D000109:Acetylcholine