Impaired vasodilator response to organic nitrates in isolated basilar arteries

1 The differential responsiveness of various sections and regions in the va scular system to the vasodilator activity of organic nitrates is important for the beneficial antiischaemic effects of these drugs. In this study we e xamined the vasodilator activity of organic nitrates in cerebral arteries, where vasodilation causes substantial nitrate induced headache. 2 Isolated porcine basilar and coronary arteries were subjected to increasi ng concentrations of glyceryl trinitrate (GTN), isosorbide-5-nitrate (ISMN) and pentaerythritol tetranitrate (PETN). S-nitroso-N-acetyl-D,L-penicillam ine (SNAP) and endothelium-dependent vasodilation was investigated for comp arison purpose. 3 The vasodilator potency (halfmaximal effective concentration in -logM) of GTN (4.33 +/- 0.1, n = 8), ISMN (1.61 +/- 0.07, n = 7) and PETN (> 10 muM, n = 7) in basilar arteries was more than 100 fold lower than that of GTN ( 6.52 +/- 0.06, n = 12), ISMN (3.66 +/- 0.08, n = 10) and PETN (6.3 +/- 0.13 , n = 8) observed in coronary arteries. 4 In striking contrast, the vasodilator potency of SNAP (halfmaximal effect ive concentration in -logM) was almost similar in basilar (7.76 +/- 0.05, n = 7) and coronary arteries (7.59 +/- 0.05, n = 9). Likewise, no difference in endothelium dependent relaxation was observed. 5 Denudation of the endothelium resulted in a small increase of the vasodil ator potency (halfmaximal effective concentration in -logM) of GTN (4.84 +/ - 0.09, n = 7, P < 0.03) in basilar arteries and similar results were obtai ned in the presence of the NO-synthase inhibitor N-omega-nitro-L-arginine ( 4.59 +/- 0.05, n = 9, P < 0.03). 6 These results suggest that cerebral conductance blood vessels such as por cine basilar arteries seems to have a reduced expression and/or activity of certain cellular enzymatic electron transport systems such as cytochrome P 450 enzymes, which are necessary to bioconvert organic nitrates to NO.