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  • Title: Effect of cumulative doses of NG-nitro-L-arginine methyl ester on coronary blood flow of anesthetized and conscious dogs.
    Author: Matsunaga T, Okumura K, Ishizaka H, Tsunoda R, Yasue H.
    Journal: Arch Int Pharmacodyn Ther; 1994; 327(3):251-65. PubMed ID: 7848010.
    Abstract:
    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.
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