Vol. 276, Issue 2, G363-G372, February 1999
Cardiac impairment and nitric oxide synthase activity in the
chronic portal vein-stenosed rat
Harold D.
Battarbee1,
James H.
Zavecz2,
Matthew B.
Grisham1,
Ronald E.
Maloney2,
L. Judson
Chandler2,
John W.
Mercer Jr.1, and
Francois M.
Cady1
Departments of 1 Molecular and
Cellular Physiology and
2 Pharmacology, Louisiana
State University Medical Center, Shreveport, Louisiana 71130-3932
Decreased cardiac
contractility and 
-adrenergic responses have been observed in the
chronic portal vein-stenosed (PVS) rat. Because nitric oxide (NO) may
be increased in PVS and has been recognized as a negative inotropic
agent, we investigated the induction of NO synthase (NOS2)
and/or changes in constitutive NOS (NOS3) as factors in the
cardiac dysfunction of the PVS rat. Ten to twelve days after portal
vein stenosis or sham operation, cardiac function was evaluated in
paced left ventricular papillary muscles (LVPM) and right ventricular
strips (RV). To determine if NO modulation of contractile function was
altered in PVS, we examined the increase in developed tension produced
by the effect of
N
-nitro-L-arginine
(L-NNA) on the myocardial
force-frequency relationship. Cardiac tissue NOS2 and NOS3 activities
were assayed, Western blot analyses of NOS2 and NOS3 expression were
performed, and circulating nitrate-nitrite
(NOX) levels (an indicator of in
vivo NOS activity) were assayed. Basal LVPM and RV contractile indexes were significantly reduced in PVS (30-50%), without a change in the relaxation rate. No between-group differences in the cardiac NOS2
or NOS3 enzymatic activities of PVS and sham-operated (SO) rats were
observed. Western blots revealed no cardiac NOS2 expression in either
SO or PVS rats. In contrast, NOS3 was expressed in both SO and PVS
rats, but there was no quantitative difference in expression between
the two groups. Changes in the cardiac force-frequency relationship
(staircase effect) after L-NNA
were consistent with NOS3 modulation of contractile function in both SO
and PVS rats, but there was no between-group difference in the
modulation. Circulating NOX
concentrations did not differ between SO and PVS rats. In conclusion,
protein expression data, enzymatic assays, end-product assays, and
functional data indicate that between-group differences in NOS2 and
NOS3 activity are not responsible for the cardiac impairment that has
been observed in the chronic PVS rat.
endotoxin; cirrhosis; liver disease; heart; constitutive nitric
oxide synthase; calcium; contractility
