Possible involvement of neuronal nitric oxide synthase enzyme in early-phase isoflurane-induced hypotension in rats

Ellenberger, Elizabeth A.; Lucas, Heather L.; Mueller, Janet L.; Barrington, Peggy L.; Chung, Eunhee; Ohgami, Yusuke; Quock, Raymond M.

doi:10.1016/j.lfs.2004.04.059

Cited by 5 publications

(1 citation statement)

References 23 publications

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“…Actually, none of the NOS inhibitors reported to date is adequately specific to achieve the pharmacological ideal of specific isoform inhibition; that is, none of these compounds can be considered absolutely selective for a given isoform. They were found only to have a relative selectivity or preference for one NOS isoform over another (12). In addition, for NOS inhibitors, there is a big difference in terms of potency and isoform selectivity between in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

Roles of nitric oxide and prostaglandins in pathogenesis of delayed colonic transit after burn injury in rats

Gan¹,

Chen²

2005

American Journal of Physiology-Regulatory, Integrative and Comp

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. Roles of nitric oxide and prostaglandins in pathogenesis of delayed colonic transit after burn injury in rats. Am J Physiol Regul Integr Comp Physiol 288: R1316-R1324, 2005. First published January 13, 2005; doi:10.1152/ajpregu.00733.2004.-Burn injury has been shown to impair gut transit, but the exact mechanism remains unknown. The present study investigated whether nitric oxide synthase (NOS) and cyclooxygenase (COX) mediated changes in burn-induced colonic transit. After rats underwent 30% total body surface area burn injury, they were injected with Smethylisothiourea (SMT, selective inducible NOS inhibitor), 7-nitronidazole (7-NI, selective neuronal NOS inhibitor), and nimesulide (NIM, selective COX-2 inhibitor), respectively. The protein and mRNA of NOS and COX-2 were measured by Western blot analysis and real-time RT-RCR, and localization of NOS and COX-2 protein was determined by immunohistochemistry. Our results showed that colonic transit assessed by the geometric center was delayed from 3.47 Ϯ 0.28 in controls to 2.21 Ϯ 0.18 after burn (P Ͻ 0.009). SMT and NIM significantly improved colonic transit in burned rats but had no effect in sham-operated rats. 7-NI failed to modify delayed transit in burned rats but significantly delayed colonic transit in shamoperated rats. Both protein and mRNA of inducible NOS and COX-2 increased significantly but not neuronal NOS in burned rats. Inducible NOS protein expression was noted not only in epithelial cells but also in neurons of the myenteric ganglia in burned rats. These findings suggest that nitric oxide (NO) produced by neuronal NOS plays an important role in mediating colonic transit under the physiological condition. NO produced by inducible NOS and prostaglandins synthesized by COX-2 are both involved in the pathogenesis of delayed colonic transit after burn injury. Inducible NOS expression in neurons of the myenteric ganglia may contribute to dysmotility with burn injury. nitric oxide synthase; cyclooxygenase; colonic motility; gastrointestinal motility COLONIC DYSMOTILITY is a common complication of burn injury. Previous studies have demonstrated that burn injury impairs colonic motility (8), but the exact mechanisms remain unknown. A potential mediator of burn-induced colonic dysmotility is nitric oxide (NO), an important nonadrenergic, noncholinergic (NANC) neurotransmitter that induces gastrointestinal smooth muscle relaxation and regulates gastrointestinal motility (6,48). NO is synthesized from L-arginine by the activation of NO synthase (NOS) (24). Three major isoforms of NOS have been identified (13): two types of constitutive NOS participate in normal physiological responses and are Ca 2ϩ /calmodulin-dependent, including neuronal NOS (nNOS), which is mainly localized to neurons (5) and endothelial NOS (eNOS), which is mainly localized to endothelium (42). The third type of NOS is called inducible NOS (iNOS), which is Ca 2ϩ /calmodulin-independent and is not present in tissues under normal physiological conditions but is expressed in a wide vari...

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Section: Discussionmentioning

confidence: 99%