Potassium channel-mediated relaxation to acetylcholine in rabbit arteries.
Endothelium-dependent relaxation is associated with smooth muscle hyperpolarization in many arteries which may account for relaxation that persists in the presence of nitric oxide inhibitors such as NG-nitro-L-arginine methyl ester (L-NAME). Acetylcholine (ACh)-induced relaxations of the rabbit thoracic and abdominal aorta and iliac and carotid arteries were studied for the relative contribution of nitric oxide-dependent and -independent mechanisms in rings suspended for measurement of isometric tension. Although relaxation of the thoracic aorta to ACh (10(-6) M) was almost blocked completely by L-NAME (3 x 10(-5) M), the maximal relaxation in the abdominal aorta, carotid and iliac arteries was only reduced by 28, 26 and 62%, respectively. In rings of abdominal aorta, L-NAME blocked the ACh-stimulated (10(-6) M) rise in cyclic GMP verifying that relaxation which persists in L-NAME-treated rings is not mediated by nitric oxide. The L-NAME resistant response was nearly abolished by elevated external K+ in rings of abdominal aorta and carotid artery, suggesting this relaxation may be mediated by a membrane potential sensitive mechanism. Furthermore, tetraethylammonium (10(-3) M) partially and charybdotoxin (5 x 10(-8) M) completely inhibited the remaining L-NAME-resistant relaxation in both abdominal aorta and carotid artery, suggesting a role for Ca(++)-activated K(+)-channels. Blockers of ATP-sensitive K+ channels also inhibited the L-NAME resistant relaxation in the abdominal aorta only.(ABSTRACT TRUNCATED AT 250 WORDS)
Cowan
C L
CL
Robert Dawson Evans Memorial Department of Clinical Research, Boston University Medical Center, Massachusetts.
Palacino
J J
JJ
Najibi
S
S
Cohen
R A
RA
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000502:physiology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D013268:Stimulation, Chemical; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology
D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D001120:Arginine; D014044:Tolbutamide; D006152:Cyclic GMP; D000109:Acetylcholine; D011188:Potassium; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester