Aorta and skeletal muscle NO synthase expression in experimental heart failure.
Nitric oxide (NO), the free radical that accounts for the biological activity 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 heart failure (CHF). The aim of this study was to investigate the expression of NOS in the descending aorta and in the skeletal muscles of rats subjected to heart failure. The alkaloid, monocrotaline, was used to induce pulmonary hypertension and cardiac failure in rats. The expression of both the constitutive (ecNOS) and the inducible (iNOS) isoforms 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/microgram total proteins, P < 0.001) whereas the expression of ecNOS in the smooth muscle is increased (from 0.024 +/- 0.004 to 0.059 +/- 0.009 OD/ microgram total proteins, P < 0.01). The total aortic ecNOS is diminished in CHF respect to control animals (0.062 +/- 0.009 v 0.107 +/- 0.013 OD/microgram total proteins, P < 0.01). On the contrary, no difference in ecNOS protein expression was observed in the extensor digitorum longus and soleus muscles. Furthermore, iNOS was not detected in any of the tissues considered. In conclusion, experimental CHF causes a re-setting of the ecNOS protein expression in the descending aorta but not in skeletal muscles. The reduced abundance of ecNOS in the aortic endothelium is consistent with the impairment of the vasodilating function reported in patients with CHF.
Comini
L
L
Fondazione Salvatore Maugeri, Clinica del Lavoro e della Riabilitazione, Gussago, Brescia, Italy.
Bachetti
T
T
Gaia
G
G
Pasini
E
E
Agnoletti
L
L
Pepi
P
P
Ceconi
C
C
Curello
S
S
Ferrari
R
R
D000818:Animals; D001011:Aorta / Q000201:enzymology*; D001201:Ascites; D001835:Body Weight; D004730:Endothelium, Vascular / Q000201:enzymology; D005260:Female; D006333:Heart Failure / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D016686:Monocrotaline / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000201:enzymology*; D009131:Muscle, Smooth, Vascular / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D009929:Organ Size; D010996:Pleural Effusion; D051381:Rats; D017207:Rats, Sprague-Dawley
D016686:Monocrotaline; D019001:Nitric Oxide Synthase