Journal of Applied Physiology, Vol 75, Issue 1 424-431, Copyright © 1993 by American Physiological Society
Effects of NG-substituted arginines on coronary vascular function after endotoxin
M. J. Winn, B. Vallet, N. K. Asante, S. E. Curtis and S. M. Cain
Department of Pharmacology, University of Alabama, Birmingham 35294.
We investigated the responses of canine coronary rings to
endothelium-derived relaxing factor-nitric oxide- (EDRF-NO) dependent
agonists and NO synthase (NOS) inhibitors 3 h after endotoxic shock was
induced in dogs by lipopolysaccharide infusion (LPS; 2 mg/kg).
EDRF-NO-dependent relaxation to thrombin [control maximum response produced
after administration of thrombin (Emax) was -85.2 +/- 7.0% of the
constrictor response produced by the thromboxane analogue U-46619],
acetylcholine (control Emax -88.4 +/- 3.4%), or bradykinin (control Emax
-80.5 +/- 2.2%) was not inhibited by LPS (Emax thrombin -75.9 +/- 9.5%;
Emax acetylcholine -90.2 +/- 2.4%; Emax bradykinin -91.6 +/- 3.4%). The NOS
inhibitor NG-monomethyl-L-arginine (L-NMMA) (10(-6)-3 x 10(-4) M) caused
constriction of rings with endothelium (Emax 36.3 +/- 5.6%), an effect that
was greater after LPS (Emax 59.2 +/- 4.1%; P < 0.05). D-NMMA had no
effect in control, but it increased tension after LPS (Emax 20.8 +/- 9.7%).
Contrary to expectations, L- and D-NMMA relaxed endothelium-denuded rings
(-30.4 +/- 8.7% L-NMMA; -45.1 +/- 11.7% D-NMMA; P < 0.05). However,
neither agent caused relaxation after in vivo LPS (10.2 +/- 3.4% L-NMMA;
8.9 +/- 5.2% D-NMMA). N omega-nitro-L-arginine-methylester (L-NAME) and
nitro-L-arginine (10(-6)-3 x 10(-4) M) increased tension (Emax 82.3 +/-
23.9 and 73.1 +/- 8.8%, respectively) but only when endothelium was
present, and the increases were no greater in LPS-treated groups than in
controls (with LPS: Emax L-NAME 87.3 +/- 16.5%; Emax nitro-L-arginine 65.7
+/- 3.3%).(ABSTRACT TRUNCATED AT 250 WORDS)
