Divergent biological actions of coronary endothelial nitric oxide during progression of cardiac hypertrophy

Coronary endothelial NO synthase expression and NO bioactivity were investigated at sequential stages during the progression of left ventricular hypertrophy. Male guinea pigs underwent abdominal aortic banding or sham operation. Left ventricular contractile function was quantified in isolated ejecting hearts. Coronary endothelial and vasodilator function were assessed in isolated isovolumic hearts in response to boluses of bradykinin (0.001 to 10 mu mol/L), substance P (0.01 to 100 mu mol/L), diethylamine NONOate (DEA-NO) (0.1 to 1000/mu mol/L), N-G-monomethyl-L-arginine monoacetate (L-NMMA) (10 mmol/L), and adenosine (10 mmol/L). At a stage of compensated left ventricular hypertrophy (3 weeks), left ventricular endothelial NO synthase protein expression was unaltered (Western blot and immunocytochemistry). Vasoconstriction in response to L-NMMA was increased in banded animals compared with sham-operated animals (13.8 +/-2.1% versus 6.2 +/-1.3%, n=10; P0.4 densitometric units; sham-operated animals, 12.2 +/-1.7 densitometric units; n=5; P2.4% versus 39.7 +/-2.2%, n=10; P1.8% versus 34.6 +/-1.8%, n=10; P2.0% versus 35.7 +/-2.0%, n=10; P