Comparison of nitroprusside and nitroglycerin in inhibition of angiotensin II and other vasoconstrictor-mediated contraction in human coronary bypass conduits

Abstract

AIMS: To compare the effect of nitroprusside (SNP) and nitroglycerin (NTG) on angiotensin II (ANGII), endothelin-1 (ET-1), and alpha1-adrenoceptor (phenylephrine, PE)-mediated contraction in internal mammary artery (IMA). METHODS: Human IMA segments (n=120) taken from 37 patients were studied. Concentration-relaxation curves for SNP and NTG were established in IMA precontracted with these vasoconstrictors. Concentration-contraction curves were also constructed in IMA rings incubated with SNP and NTG (0.1 and 1 microM) for 10 min. RESULTS: Both SNP and NTG caused full relaxation with similar EC50s except NTG was four-fold more potent than SNP in PE-induced contraction (-7.92 +/- 0.06 vs -7.32 +/- 0.2 log M, mean +/- s.e. mean, P<0.01; 95% confidence interval for the difference of the means: 0.19, 1.01 log M). Pretreatment with SNP (0.1 and 1 microM) significantly depressed the contraction by ANGII from 56.6 +/- 7.7% (of 100 mM K+-contraction) to 18.3 +/- 8.6% and 3.9 +/- 2.1% (P=0.0001). In four rings treated with SNP, the contraction to ANGII was abolished whereas NTG did not depress ANGII-mediated contraction. Pretreatment with SNP (1 microM), but not NTG, significantly depressed the magnitude of the PE-induced contraction from 4.7 +/- 1.2 to 1.7 +/- 0.4 g (P<0.05). Treatment with both SNP and NTG significantly increased the EC50 (-5.09 +/- 0.17 log M, P=0.0007 for SNP and -5.40 +/- 0.06 log M, P=0.02 for NTG). Pretreatment with SNP did not significantly change either the magnitude or the EC50 of the ET-1-induced contraction. CONCLUSIONS: SNP may be advantageous compared with NTG in preventing coronary arterial graft contraction. However, once grafts have constricted to ANGII, alpha1-adrenoceptor agonists, and ET-1, NTG may be only marginally advantageous.