Effect of cumulative doses of NG-nitro-L-arginine methyl ester on coronary blood flow of anesthetized and conscious dogs.
To examine the effect of cumulative doses of NG-nitro-L-arginine methyl ester (LNAME), an inhibitor of nitric oxide synthesis, on coronary blood flow, basal left circumflex artery blood flow and acetylcholine-induced flow increment were observed in anesthetized and conscious dogs. Four doses of LNAME (10(-5) M, 10(-4) M, 10(-3) M and 10(-2) M in the left circumflex artery blood were cumulatively infused into the left circumflex artery. All dogs were pretreated with 8-phenyltheophylline and acetylsalicylic acid to inhibit endogenous adenosine and vasodilator prostaglandin, respectively. In anesthetized dogs (n = 10), systolic blood pressure was increased with 10(-2) M of LNAME and heart rate was decreased with > or = 10(-3) M of LNAME. All doses of LNAME significantly decreased the left circumflex artery blood flow in a dose-dependent manner, without affecting the rate-pressure product. The acetylcholine-induced flow increment was significantly attenuated with all doses of LNAME. However, no further attenuation was induced by > or = 10(-3) M of LNAME and the maximal dose did not completely abolish the effect of acetylcholine. In conscious dogs (n = 7), LNAME showed similar effects to those seen in anesthetized dogs: the left circumflex artery blood flow decreased with > or = 10(-4) M of LNAME, without affecting the rate-pressure product; the acetylcholine-induced flow increment was attenuated with > or = 10(-4) M of LNAME, but not completely abolished. Thus, there is a basal nitric oxide release from the endothelium in the coronary resistance vessels of anesthetized and conscious dogs. However, (an)other mechanism(s) than the L-arginine-nitric oxide pathway seem(s) to be involved in the acetylcholine-induced vasodilatation.
Division of Cardiology, Kumamoto University School of Medicine, Japan.
T
T
Matsunaga
K
K
Okumura
H
H
Ishizaka
R
R
Tsunoda
H
H
Yasue
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000037:antagonists & inhibitors; D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D011448:Prostaglandin Antagonists; D009569:Nitric Oxide; D001120:Arginine; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine; D000109:Acetylcholine; D001241:Aspirin; D019331:NG-Nitroarginine Methyl Ester