Nitric oxide synthase 1 is partly compensating for nitric oxide synthase 3 deficiency in nitric oxide synthase 3 knock‐out mice and is elevated in murine and human cirrhosis

Biecker, Erwin; Neef, Markus; Sägesser, Hans; Shaw, Sidney; Koshy, Abraham; Reichen, Jürg

doi:10.1111/j.1478-3231.2004.0933.x

Cited by 29 publications

(14 citation statements)

References 62 publications

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“…Xu and colleagues (35) showed that 7-NI blocked the development of hyperdynamic circulation in cirrhotic rats. Furthermore, increased nNOS mRNA and/or protein levels have been documented in aortae of BDL mice (3), mesenteric arteries of portal hypertensive rats (10), and hepatic arteries of cirrhotic patients (3). Finally, a preeminent role of nNOS would explain the persistence of hyperdynamic circulation in portal hypertensive double-knockout mice lacking the genes for both eNOS and inducible NOS (8) and cirrhotic knockout mice lacking the eNOS gene (12).…”

Section: Discussionmentioning

confidence: 95%

Altered mesenteric venous capacitance and volume pooling in cirrhotic rats are mediated by nitric oxide

Yang

Liu²,

Gaskari³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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In cirrhosis, despite augmented blood volume, effective circulating volume is decreased. This implies abnormal regulation of blood volume, i.e., venous pooling. Because gut veins are the main blood reservoir, we studied mesenteric venous capacitance and compliance in a rat model of cirrhosis. Cirrhosis was induced by bile duct ligation (4 wk). Controls were sham operated. Changes in first-order mesenteric vein diameters induced by drugs, hemorrhage, and stepwise increases in portal pressure (inflatable cuff) were directly observed by intravital microscopy. Effects of nitric oxide on responses to acute graded hemorrhage were studied by use of selective NO synthase (NOS) isoform inhibitors. Pressures were related to diameters to assess capacitance and compliance. Compared with controls, cirrhotic rats demonstrated increased mesenteric venous capacitance and decreased compliance. Norepinephrine induced venoconstriction but did not affect compliance. Prazosin markedly diminished compliance in controls but not cirrhotics. Conversely, the nonspecific NOS inhibitor N-nitro-l-arginine methyl ester (l-NAME) decreased compliance in cirrhotics, but not controls. Tetrodotoxin venodilated controls, venoconstricted cirrhotics, and markedly decreased compliance in both groups. When hemorrhaged, controls rapidly venoconstricted to compensate for initial hypotension, whereas cirrhotic rats remained hypotensive because venoconstriction was severely blunted. Pretreatment with l-NAME or the selective neuronal NOS inhibitors S-methyl-l-thiocitrulline and 7-nitroindazole normalized the homeostatic responses of cirrhotic rats, whereas the selective endothelial-constitutive NOS inhibitor N-iminoethyl-l-ornithine did not affect the response. In conclusion, mesenteric veins of cirrhotic rats showed enhanced capacitance, attenuated compensatory constrictive response to hemorrhage, and decreased compliance. The first two abnormalities were caused by neuronal NOS-derived nitric oxide.

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Section: Discussionmentioning

confidence: 95%

Altered mesenteric venous capacitance and volume pooling in cirrhotic rats are mediated by nitric oxide

Yang

Liu²,

Gaskari³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…It is well-known that NO is an important physiologic mediator of erectile function derived from nonadrenergic noncholinergic neurotransmission [52]. However, excess NO is involved in the pathogenesis of hepatic [53,54] and extrahepatic [55,56] manifestations of cirrhosis. In the current study, the penile NO was over-expressed in bile duct ligated rats.…”

Section: Discussionmentioning

confidence: 99%

Ursodeoxycholic acid alleviates cholestasis-induced histophysiological alterations in the male reproductive system of bile duct-ligated rats

Saad

Mahmoud

2014

Reproductive Toxicology

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“…This is phenomenon is well-established, for example, by several studies in other models showing that the deletion of eNOS results in increased expression of nNOS isoform [76][77][78][79]. It is less clear; however, whether this isoform compensation occurs in the case of iNOS deletion strategies.…”

Section: Limitationsmentioning

confidence: 80%

The complex role of iNOS in acutely rejecting cardiac transplants

Pieper

Roza

2008

Free Radical Biology and Medicine

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This review summarizes the evidence for a detrimental role of nitric oxide (NO) derived from inducible NO synthase (iNOS) and/or reactive nitrogen species such as peroxynitrite in acutelyrejecting cardiac transplants. In chronic cardiac transplant rejection, iNOS may have an opposing beneficial component. The purpose of this review is primarily to address issues related to acute rejection which is a recognized risk factor for chronic rejection. The evidence for a detrimental role is based upon strategies involving non-selective NOS inhibitors, NO neutralizers, selective iNOS inhibitors and iNOS gene deletion in rodent models of cardiac rejection. The review is discussed in the context of the impact on various components including graft survival, histological rejection and cardiac function which may contribute in toto to the process of graft rejection. Possible limitations of each strategy are discussed in order to understand better the variance in published findings including issues related to the potential importance of cell localization of iNOS expression. Finally, the concept of a dual role of NO and its down-stream product, peroxynitrite, in rejection vs. immune regulation is discussed.

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Nitric oxide synthase 1 is partly compensating for nitric oxide synthase 3 deficiency in nitric oxide synthase 3 knock‐out mice and is elevated in murine and human cirrhosis

Cited by 29 publications

References 62 publications

Altered mesenteric venous capacitance and volume pooling in cirrhotic rats are mediated by nitric oxide

Altered mesenteric venous capacitance and volume pooling in cirrhotic rats are mediated by nitric oxide

Ursodeoxycholic acid alleviates cholestasis-induced histophysiological alterations in the male reproductive system of bile duct-ligated rats

The complex role of iNOS in acutely rejecting cardiac transplants

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