Gallbladder Hyporesponsiveness to An Exogenous Nitric Oxide Donor, Glyceryl Trinitrate, in Patients With Advanced Liver Cirrhosis

Cirrhosis is typically associated with a hyperdynamic circulation consisting of low blood pressure, low systemic vascular resistance (SVR), and high cardiac output. We have recently reported that nonspecific inhibition of nitric oxide synthase (NOS) with nitro-l-arginine methyl ester reverses the hyperdynamic circulation in rats with advanced liver cirrhosis induced by carbon tetrachloride (CCl4). Although an important role for endothelial NOS (eNOS) is documented in cirrhosis, the role of neuronal NOS (nNOS) has not been investigated. The present study was carried out to specifically investigate the role of nNOS during liver cirrhosis. Specifically, physiological, biochemical, and molecular approaches were employed to evaluate the contribution of nNOS to the cirrhosis-related hyperdynamic circulation in CCl4-induced cirrhotic rats with ascites. Cirrhotic animals had a significant increase in water and sodium retention. In the aorta from cirrhotic animals, both nNOS protein expression and cGMP concentration were significantly elevated compared with control. Treatment of cirrhotic rats for 7 days with the specific nNOS inhibitor 7-nitroindazole (7-NI) normalized the low SVR and mean arterial pressure, elevated cardiac index, and reversed the positive sodium balance. Increased plasma arginine vasopressin concentrations in the cirrhotic animals were also repressed with 7-NI in association with diminished water retention. The circulatory changes were associated with a reduction in aortic nNOS expression and cGMP. However, 7-NI treatment did not restore renal function in cirrhotic rats (creatinine clearance: 0.76 ± 0.03 ml · min−1· 100 g body wt−1in cirrhotic rats vs. 0.79 ± 0.05 ml · min−1· 100 g body wt−1in cirrhotic rats+7-NI; P NS.). Taken together, these results indicate that nNOS-derived NO contributes to the development of the hyperdynamic circulation and fluid retention in cirrhosis.

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Glyceryl trinitrate, a nitric oxide donor, abrogates ferric nitrilotriacetate-induced oxidative stress and renal damage

Archives of Biochemistry and Biophysics ◽

10.1016/s0003-9861(03)00365-5 ◽

2003 ◽

Vol 418 (1) ◽

pp. 71-79 ◽

Cited By ~ 13

Author(s):

Ayesha Rahman ◽

Salahuddin Ahmed ◽

Shaista M Vasenwala ◽

Mohammad Athar

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Glyceryl Trinitrate ◽

Renal Damage ◽

Nitric Oxide Donor ◽

Ferric Nitrilotriacetate

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Myocardial relaxant effect of exogenous nitric oxide in isolated ejecting hearts

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1994.266.5.h1699 ◽

1994 ◽

Vol 266 (5) ◽

pp. H1699-H1705 ◽

Cited By ~ 15

Author(s):

R. Grocott-Mason ◽

S. Fort ◽

M. J. Lewis ◽

A. M. Shah

Keyword(s):

Nitric Oxide ◽

Sodium Nitroprusside ◽

Coronary Flow ◽

Systolic Function ◽

Myocardial Contraction ◽

Left Ventricular ◽

Nitric Oxide Donor ◽

Vasodilator Activity ◽

Exogenous Nitric Oxide ◽

Whole Heart

In isolated myocytes and papillary muscles, both nitric oxide, acting through guanosine 3',5'-cyclic monophosphate (cGMP), and cGMP analogues exert a novel effect on myocardial contraction, influencing mainly the onset of relaxation. We studied the effect of the exogenous nitric oxide donor, sodium nitroprusside (0.1-10 microM), in isolated ejecting guinea pig hearts at constant filling pressure, afterload, and heart rate to identify its direct myocardial effects in the whole heart. Sodium nitroprusside induced concentration-dependent increases in coronary flow as well as premature and faster early left ventricular (LV) pressure decline, but did not change end-diastolic or peak LV pressure or peak rate of rise of LV pressure. There was no correlation between changes in coronary flow and LV pressure decline. Sodium nitroprusside effects were inhibited by hemoglobin, which inactivates nitric oxide. The cGMP-independent vasodilator nicardipine also increased coronary flow but did not influence early LV pressure fall. Thus exogenous nitric oxide exerts novel direct myocardial relaxant effects in the isolated ejecting heart, independent of its known vasodilator activity, and without compromising systolic function.

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