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一氧化氮抑制对血压的影响取决于大鼠品系。

The effect of nitric oxide inhibition on blood pressure depends on rat strain.

作者信息

Forster J, Beebe P, Wang H, Wood J G

机构信息

Department of Surgery, University of Kansas Medical Center, Kansas City, Kansas 66160-7309, USA.

出版信息

J Surg Res. 2001 Apr;96(2):218-23. doi: 10.1006/jsre.2001.6087.

DOI:10.1006/jsre.2001.6087
PMID:11266276
Abstract

BACKGROUND

Nitric oxide is a continuously released endothelium-derived vasodilator and plays an important role in the maintenance of blood pressure (BP). Rat strains appear to differ in their resting BP and their response to the intravenous administration of N(omega)-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase inhibitor. The presence of diabetes and hypertension also leads to differences in BP responses to l-NAME. We postulated that the contribution of NO to resting BP varies between rat strains and certain strains may be more sensitive to the effects of NO blockade.

METHODS

Blood pressure was continuously measured using a carotid arterial catheter and the responses to l-NAME were compared in anesthetized Lewis and Sprague-Dawley rats during a 2-h control period and a 2-h experimental period. l-NAME was given by a 50 mg/kg bolus followed by a 10 mg/kg/h infusion via a mesenteric vein.

RESULTS

During the control period, the Lewis animals had lower systolic and diastolic BPs of 103 +/- 1 and 80 +/- 1 mm Hg compared with 127 +/- 1 and 105 +/- 1 mm Hg measured in Sprague-Dawley rats (P < 0.01). Although l-NAME infusion increased systolic BP in both strains compared with control values (P < 0.00005), the magnitude was significantly greater in Sprague-Dawley than Lewis animals (P = 0.0142); additionally, the BP was unstable in the Lewis animals. Furthermore, pulse pressure decreased during l-NAME in Lewis animals but increased in Sprague-Dawley animals (P < 0.00005). There were no significant changes in serum concentrations of aspartate transaminase nor of nitrite plus nitrate after l-NAME in either group.

CONCLUSION

These results indicate that the effect of l-NAME on systemic BP differs markedly in Sprague-Dawley and Lewis rats, suggesting that the role of nitric oxide in regulation of resting vascular resistance may differ significantly between these rat strains. Rat strain is an important consideration for valid comparisons between studies.

摘要

背景

一氧化氮是一种持续释放的内皮源性血管舒张剂,在维持血压(BP)方面发挥着重要作用。大鼠品系在静息血压以及对静脉注射一氧化氮合酶抑制剂N(ω)-硝基-L-精氨酸甲酯(L-NAME)的反应方面似乎存在差异。糖尿病和高血压的存在也会导致对L-NAME的血压反应出现差异。我们推测,一氧化氮对静息血压的贡献在不同大鼠品系之间有所不同,并且某些品系可能对一氧化氮阻断的影响更为敏感。

方法

使用颈动脉导管连续测量血压,并在麻醉的Lewis大鼠和Sprague-Dawley大鼠的2小时对照期和2小时实验期内比较对L-NAME的反应。通过肠系膜静脉以50mg/kg的推注剂量给予L-NAME,随后以10mg/kg/h的速度输注。

结果

在对照期,Lewis大鼠的收缩压和舒张压较低,分别为103±1mmHg和80±1mmHg,而Sprague-Dawley大鼠的收缩压和舒张压分别为127±1mmHg和105±1mmHg(P<0.01)。尽管与对照值相比,输注L-NAME后两个品系的收缩压均升高(P<0.00005),但Sprague-Dawley大鼠的升高幅度明显大于Lewis大鼠(P = 0.0142);此外,Lewis大鼠的血压不稳定。此外,Lewis大鼠在输注L-NAME期间脉压降低,而Sprague-Dawley大鼠的脉压升高(P<0.00005)。两组在输注L-NAME后,天冬氨酸转氨酶以及亚硝酸盐加硝酸盐的血清浓度均无显著变化。

结论

这些结果表明,L-NAME对全身血压的影响在Sprague-Dawley大鼠和Lewis大鼠中存在显著差异,这表明一氧化氮在调节静息血管阻力中的作用在这些大鼠品系之间可能存在显著差异。大鼠品系是不同研究之间进行有效比较时的一个重要考虑因素。

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