LACK OF CORRELATION BETWEEN MYOCARDIAL NITRIC-OXIDE AND CYCLIC GUANOSINE-MONOPHOSPHATE CONTENT IN BOTH NITRATE-TOLERANT AND NITRATE-NONTOLERANT RATS

We studied the effect of nitroglycerin (NTG) on cardiac nitric oxide ( NO) and cyclic guanosine monophosphate (cGMP) content in nitrate-toler ant/nontolerant rats in vivo. The effect of the pharmacological blocka de of endogenous NO synthesis and the effect of exogenous NO on cardia c cGMP were also examined. Rats were treated with 100 mg/kg of NTG and corresponding vehicle s.c. three times a day for 2.5 days to induce N TG-tolerance/nontolerance. Rats were then administered a single dose o f s.c. 100 mg/kg of NTG to test the effect of NTG in tolerant/nontoler ant states, respectively. Nontolerant rats treated with vehicle were c ontrols, and nontolerant rats treated with the NO synthesis inhibitor NG-nitro-L-arginine (LNNA, 20 mg/kg) were negative controls. Another g roup of nontolerant rats treated i.v. with the direct NO donor sodium nitroprusside (SNP, 3 mg/kg) were positive controls. Cardiac NO assess ed by electron spin resonance after In vivo spin-trapping increased 10 0-fold (P < 0.05) in the positive control, 10-fold (P < 0.05) in the N TG-tolerant group, and di-fold (P < 0.05) in the single NTG group, whe n compared to controls. In the negative control group, NO was reduced to near the detection limit (four-fold reduction, P < 0.05). Cardiac c GMP measured by radioimmunoassay was increased significantly (two-fold , P < 0.05) only in the positive control group,and there were no diffe rences among the other groups. This shows that: 1) in vivo cardiac bio conversion of NTG to NO is not impaired in nitrate tolerance; and 2) c hanges in cardiac NO content are not reflected by changes in cGMP cont ent in nitrate-tolerant and -nontolerant rats. (C) 1998 Elsevier Scien ce Inc.