RELATIONSHIP BETWEEN CGMP AND MYOCARDIAL O-2 CONSUMPTION IS ALTERED IN T-4-INDUCED CARDIAC-HYPERTROPHY

We tested the hypothesis that increases in guanosine 3',5'-cyclic mono phosphate (cGMP) would reduce myocardial Oz consumption and that thyro xine (T-4)-induced (0.5 mg/kg for 16 days) cardiac hypertrophy would c hange this relationship. Anesthetized open-chest New Zealand White rab bits were divided into four groups: control vehicle (CV, n = 7), contr ol nitroprusside (CN, n = 6), T-4 vehicle (T4V, n = 8), and T-4 nitrop russide (T4N, n = 8). Vehicle or sodium nitroprusside (10(-4) M) was t opically applied to the left ventricular subepicardium for 15 min. Cor onary blood flow (radioactive microspheres) and O-2 extraction (micros pectrophotometry) were used to determine O-2 consumption. Guanylate cy clase activity and cGMP were determined by radioimmunoassay. T-4 incre ased the heart weight-to-body weight ratio from 2.7 +/- 0.1 to 3.4 +/- 0.2. Topical application of nitroprusside had no significant hemody- namic effects. Nitroprusside significantly increased myocardial cGMP i n control hearts (CV = 4.1 +/- 0.3 to CN = 12.4 +/- 5.0 pmol/g) and T- 4 hearts (T4V = 3.9 +/- 0.3 to T,N = 5.2 +/- 0.4). The increase in the level of myocardial cGMP was significantly greater in CN (+202%) than in T4N (+33%). There were no significant differences in basal or tota l guanylate cyclase activity between control and T-4 rabbits. Myocardi al O-2 consumption significantly declined in both groups during nitrop russide (10.8 +/- 1.4 for CV to 7.3 +/- 1.0 for CN (-32%) and 13.6 +/- 1.2 for T4V to 9.9 +/- 1.4 ml O-2.min(-1).100 g(-1) for T4N (-27%)). Thus, although basal levels of cGMP were not altered, T-4-treated hear ts responded to nitroprusside with a lesser increase in cGMP, and O-2 consumption was diminished similarly. This indicates a change in the i nverse relationship between the myocardial level of cGMP and O-2 consu mption with T-4.