NITRIC-OXIDE INHIBITION IN AN OVINE MODEL OF HEART-FAILURE

1. The role of nitric oxide (NO) in congestive heart failure was inves tigated by studying the acute haemodynamic, hermonal and renal effects of N-G-monomethyl-L-arginine (L-NMMA), a nitric oxide inhibitor, give n as incremental bolus doses in six sheep before (normal) and after in duction of heart failure (HF) by rapid left ventricular pacing (LVP). 2. L-NMMA caused significant initial dose-dependent rises in left vent ricular systolic pressure, mean arterial pressure (MAP), peripheral re sistance (PR) and left atrial pressure and declines in cardiac output in both normal and HF states (maximum response in 2-6 min), These resp onses were all but abolished when L-arginine was given concurrently wi th L-NMMA, The dose-response curve for the L-NMMA-induced rise in MAP was shifted to the right following LVP (P < 0.05), which is consistent with previous observations of blunted NO synthase activity in HF. A s ubsequent decline in MAP and PR to below prebolus levels was observed 30-60 min after L-NMMA administration in the paced state, No significa nt hormonal or renal effects were observed. 3. In conclusion, the pres ent study confirms the important haemodynamic role played by endogenou s NO in the normal state and demonstrates a blunted presser response t o NO inhibition in this model of heart failure.