Nitroglycerin dilates coronary collateral vessels during exercise after blockade of endogenous NO production

In a previous study nitroglycerin failed to dilate coronary collateral vess els during exercise. This study tested the hypothesis that failure of nitro glycerin to increase collateral flow occurred because endogenous nitric oxi de (NO) had activated the guanylate cyclase vasodilator pathway so that add itional NO from nitroglycerin could have no additional effect. Six dogs wer e collateralized using intermittent 2-min occlusions of the left anterior d escending coronary artery followed by permanent occlusion. One week after p ermanent coronary occlusion, dogs were exercised on a treadmill (heart rate 202 +/- 5 boats/min), while blood flow was measured with radioactive micro spheres. Blood flow to the collateral zone during control exercise was 1.90 +/- 0.11 ml min(-1) g(-1) compared with 2.28 +/- 0.15 ml.min(-1).g(-1) in the normal zone (P < 0.05); systolic wall thickening was 23 +/- 3% in the c ollateral zone compared with 27 +/- 2% in the normal zone. When NG-nitro-L- arginine (L-NNA; 20 mg/kg iv) was administered to block NO production, coll ateral zone flow during exercise decreased to 1.43 +/- 0.20 ml min(-1) g(-1 ) (P < 0.05), and systolic wall thickening decreased to 12 +/- 4% (P < 0.05 ). A subsequent infusion of nitroglycerin (2 mu g.kg(-1). min(-1) iv) incre ased collateral zone blood flow to 1.65 +/- 0.16 ml.min(-1).g(-1) (P < 0.05 ) and increased systolic wall thickening to 22 +/- 5% (P < 0.05). These fin dings demonstrate that endogenous NO contributes to collateral zone blood f low during exercise. if endogenous NO synthesis is blocked, then nitroglyce rin is effective in improving collateral zone blood flaw and contractile fu nction during exercise.