AORTA AND SKELETAL-MUSCLE NO SYNTHASE EXPRESSION IN EXPERIMENTAL HEART-FAILURE

Nitric oxide (NO), the free radical that accounts for the biological a ctivity of endothelium-derived relaxing factor, is synthesized from L- arginine by NO synthase (NOS), There is evidence that NO availability is reduced in the peripheral vasculature of patients with congestive h eart failure (CHF), The aim of this study was to investigate the expre ssion of NOS in the descending aorta and in the skeletal muscles of ra ts subjected to heart failure, The alkaloid, monocrotaline, was used t o induce pulmonary hypertension and cardiac failure in rats, The expre ssion of both the constitutive (ecNOS) and the inducible (iNOS) isofor ms of the enzyme was assessed by Western blot analysis, In CHF animals , the ecNOS location in the aorta is altered: the endothelial protein expression is substantially reduced (from 0.083 +/- 0.012 to 0.003 +/- 0.004 OD/mu g total proteins, P<0.001) whereas the expression of ecNO S in the smooth muscle is increased (from 0.024 +/- 0.004 to 0.053 +/- 0.009 OD/ mu g total proteins, P<0.01). The total aortic ecNOS is dim inished in CHF respect to control animals (0.062 +/- 0.009 v 0.107 +/- 0.013 OD/mu g total proteins, P<0.01), On the contrary, no difference in ecNOS protein expression was observed in the extensor digitorum lo ngus and soleus muscles. Furthermore, iNOS was not detected in any of the tissues considered, In conclusion, experimental CHF causes a re-se tting of the ecNOS protein expression in the descending aorta but not in skeletal muscles, The reduced abundance of ecNOS in the aortic endo thelium is consistent with the impairment of the vasodilating function reported in patients with CHF, (C) 1996 Academic Press Limited