Nitric oxide synthase in porcine heart mitochondria: evidence for low physiological activity

The capacity of isolated porcine heart mitochondria to produce nitric oxide (NO) via mitochondrial NO synthase (NOS) was evaluated. The mitochondrial NOS content and activity (0.2 nmol NO.mg mitochondrial protein(-1).min(-1)) were similar to 10 times lower than previously reported for the rat liver. No evidence for mitochondrial NOS-generated NO was found in mitochondrial suspensions based on the lack of NO production and the lack of effect of ei ther L-arginine or NOS inhibitors on the rate of respiration. The reason th at even the low mitochondrial NOS activity did not result in net NO product ion and metabolic effects is because the mitochondrial metabolic breakdown of NO (1-4 nmol NO.mg mitochondrial protein(-1).min(-1)) was greater than t he maximum rate of NO production measured in homogenates. These data sugges t that NO production at the mitochondria via NOS is not a significant sourc e of NO in the intact heart and does not regulate cardiac oxidative phospho rylation.