Contribution of activation of K+ channels to glyceryl trinitrate-induced relaxation of rabbit aorta.
1. Possible contribution of K+ channel opening to the relaxation by glyceryl trinitrate (GTN) was examined using isolated rabbit aorta. 2. While glibenclamide and apamin failed to affect relaxation by GTN, both charybdotoxin (ChTx) and iberiotoxin (IbTx) effectively attenuated GTN-induced relaxation. 3. The increase in cGMP produced by GTN was not attenuated by ChTx and IbTx. 4. The inhibitory effect of ChTx on GTN-induced relaxation was not reduced in the presence of zaprinast, indicating that cGMP but not GMP was responsible for activation of the K+ channel. 5. Okadaic acid, a selective inhibitor of protein phosphatase 2A, had no effect on the relaxation by GTN. These results indicate that, though small in degree, activation of a ChTx-sensitive K+ channel (large conductance Ca(2+)-activated K+ channel) is involved in the GTN-induced relaxation in rabbit aorta.
Ishibashi
T
T
Department of Pharmacology, Niigata University School of Medicine, Japan.
Kawada
T
T
Kato
K
K
Hamaguchi
M
M
Imai
S
S
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001030:Apamin / Q000494:pharmacology; D018999:Charybdotoxin; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology; D004988:Ethers, Cyclic / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D005996:Nitroglycerin / Q000494:pharmacology*; D019319:Okadaic Acid; D010455:Peptides / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D054648:Protein Phosphatase 2; D011688:Purinones / Q000494:pharmacology; D011817:Rabbits; D012604:Scorpion Venoms / Q000494:pharmacology
D004988:Ethers, Cyclic; D010455:Peptides; D015221:Potassium Channels; D011688:Purinones; D012604:Scorpion Venoms; D018999:Charybdotoxin; D019319:Okadaic Acid; D001030:Apamin; C064719:iberiotoxin; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D005996:Nitroglycerin; C011145:zaprinast; D006152:Cyclic GMP; D005905:Glyburide