Potentiation to vasodilators by nitric oxide synthase blockade in superior mesenteric but not hepatic artery.
Our objective was to determine the vasodilator effect of adenosine and isoproterenol on the hepatic artery (HA) and superior mesenteric artery (SMA) before and after blockade of nitric oxide (NO) production to evaluate the possibility of organ specificity. Vascular circuits supplied blood flow to the liver or intestine in cats under pentobarbital sodium anesthesia. The NO synthase (NOS) antagonist N(G)-nitro-L-arginine methyl ester (L-NAME; 2.5 mg/kg iv) increased arterial pressure from 106.4 +/- 7.6 to 141.4 +/- 8.1 mmHg and raised basal vascular tone in the SMA but not in the HA. The NOS substrate L-arginine (75 mg/kg) reversed these effects. The decrease in perfusion pressure in response to adenosine was 51.7 +/- 2.9, 135.2 +/- 6.1, and 16.7 +/- 2.4 mmHg, respectively, for control and after L-NAME and L-arginine. Isoproterenol was also potentiated in the SMA. Adenosine and isoproterenol were not potentiated in the HA by L-NAME. Potentiation did not occur when HA or SMA basal tone was elevated by norepinephrine. In conclusion, L-NAME increased basal tone for the SMA and potentiated the dilation induced by adenosine and isoproterenol in the SMA but not in the HA. This study provides evidence that there is a highly organ-specific compensatory mechanism in which the absence of NO promotes potentiation of other vasodilators.
Macedo
M P
MP
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Lautt
W W
WW
D000241:Adenosine / Q000008:administration & dosage*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002415:Cats; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D006499:Hepatic Artery; D007422:Intestines / Q000098:blood supply*; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology; D008099:Liver / Q000098:blood supply*; D008297:Male; D017538:Mesenteric Artery, Superior; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D014664:Vasodilation / Q000187:drug effects*
D004791:Enzyme Inhibitors; D001120:Arginine; D019001:Nitric Oxide Synthase; D000241:Adenosine; D007545:Isoproterenol; D019331:NG-Nitroarginine Methyl Ester