Cardiovascular and Renal Actions of Cytochrome P-450 Metabolites of Arachidonic Acid

Cytochrome P-450 is the terminal oxidase of the electron transport chain in the endoplasmic reticulum. Arachidonic acid (AA) can be oxidatively metabolized by cytochrome P-450 hemoproteins to an array of compounds identified as constituents of tissues and biological fluids. Their synthesis can be manipulated by pharmacologic probes and are altered in pathophysiologic conditions. These novel eicosanoids stimulate release of peptide and steroid hormones, inhibit platelet and leukocyte aggregation, influence Na+-K+-ATPase and alter vasomotor tone. They also participate in fluid and electrolyte homeostasis, stimulus-secretion coupling, and regulation of tissue blood flow. Since these novel AA metabolites may participate in receptor-mediated signal transduction, and have been implicated in the generation of second messengers and changes in intracellular calcium, these studies have important implications for understanding basic biological mechanisms

Oxygen free radicals and congestive heart failure.

Plasma lipid peroxides (malondialdehyde) and thiols were measured in 45 patients with congestive heart failure and 45 controls. Malondialdehyde concentrations were significantly higher in the patients with congestive heart failure (median 9.0 nmol/ml interquartile range (IQR) 7.9-10.2) than in the controls (median 7.7 nmol/ml (IQR 6.9-9.2)). Plasma thiols were significantly lower in congestive heart failure (median 420 mumol/l (IQR 379-480)) than in the controls (median 463 mumol/l (IQR 445-525)). There was a significant but weak negative correlation between malondialdehyde and left ventricular ejection fraction (r = -0.35) and a positive correlation between plasma thiols and left ventricular ejection fraction (r = 0.39). This study provides clinical support for experimental data indicating that free radicals may be important in heart failure. It also suggests that the degree of free radical production may be linked to the severity of the disease