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NITRIC OXIDE INHIBITION IN AN OVINE MODEL OF HEART FAILURE
Author(s) -
Rademaker Miriam Tessa,
Fitzpatrick Michael Andrew,
Richards Arthur Mark,
Nicholls Michael Gary,
Charles Christopher John,
Frampton Christopher Miles,
Ikram Hamid
Publication year - 1996
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1996.tb02749.x
Subject(s) - heart failure , hemodynamics , medicine , nitric oxide , bolus (digestion) , nitric oxide synthase , cardiac output , omega n methylarginine , blood pressure , mean arterial pressure , cardiology , vascular resistance , heart rate , anesthesia , endocrinology
SUMMARY 1. The role of nitric oxide (NO) in congestive heart failure was investigated by studying the acute haemodynamic, hormonal and renal effects of N G ‐monomethyl‐ l ‐arginine ( l ‐NMMA), a nitric oxide inhibitor, given as incremental bolus doses in six sheep before (normal) and after induction of heart failure (HF) by rapid left ventricular pacing (LVP). 2. l ‐NMMA caused significant initial dose‐dependent rises in left ventricular systolic pressure, mean arterial pressure (MAP), peripheral resistance (PR) and left atrial pressure and declines in cardiac output in both normal and HF states (maximum response in 2–6 min). These responses were all but abolished when l ‐arginine was given concurrently with 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 subsequent decline in MAP and PR to below prebolus levels was observed 30–60 min after l ‐NMMA administration in the paced state. No significant hormonal or renal effects were observed. 3. In conclusion, the present study confirms the important haemodynamic role played by endogenous NO in the normal state and demonstrates a blunted pressor response to NO inhibition in this model of heart failure.