Mokuno S, Ito T, Numaguchi Y, Matsui H, Toki Y, Okumura K, Hayakawa T
Department of Internal Medicine II, Nagoya University School of Medicine, Japan.
Hypertens Res. 2001 Jul;24(4):395-401. doi: 10.1291/hypres.24.395.
In the current study, we investigated the NO-generation pathway in response to mechanical stimuli in SHR at the prehypertensive stage. To examine the role of NO in coronary autoregulation, we evaluated the effects of L-NAME on the coronary flow in SHR at both the prehypertensive and hypertensive stages. Isolated perfused hearts from 5- and 15-week-old SHR and from age-matched Wistar-Kyoto rats (WKY) were used. After stabilization at 60 mmHg, perfusion pressure was immediately raised to 90 mmHg to record the change in coronary flow for 10 min without (control) or with NO synthesis blockade by Nomega-nitro-L-arginine methyl ester (L-NAME). NOx- (nitrite/nitrate) was measured in coronary effluent. At 5 weeks of age, SHR did not have hypertension, while the coronary autoregulation was enhanced. L-NAME did not affect this enhanced autoregulation in 5-week-old SHR. At perfusion pressures of both 60 and 90 mmHg, 5-week-old SHR showed less coronary NOx- production than age-matched WKY. At 15 weeks, SHR showed a higher blood pressure than WKY. The coronary autoregulation in SHR remained higher than that in WKY, but was below that in 5-week-old SHR. NOx- production in 15-week-old SHR recovered to the level of age-matched WKY. These results indicate that NOx- production induced by mechanical stimulation was markedly reduced in 5-week-old SHR at the prehypertensive stage, which may have enhanced coronary autoregulation. An impaired nitric oxide production may precede the onset of hypertension in SHR.
在本研究中，我们调查了高血压前期SHR（自发性高血压大鼠）对机械刺激的一氧化氮生成途径。为了研究一氧化氮在冠状动脉自动调节中的作用，我们评估了L-硝基精氨酸甲酯（L-NAME）对高血压前期和高血压期SHR冠状动脉血流的影响。使用了来自5周龄和15周龄SHR以及年龄匹配的Wistar-Kyoto大鼠（WKY）的离体灌注心脏。在稳定于60 mmHg后，灌注压力立即升至90 mmHg，记录无（对照）或用Nω-硝基-L-精氨酸甲酯（L-NAME）阻断一氧化氮合成时10分钟内冠状动脉血流的变化。测量冠状动脉流出液中的NOx-（亚硝酸盐/硝酸盐）。5周龄时，SHR没有高血压，但其冠状动脉自动调节增强。L-NAME对5周龄SHR这种增强的自动调节没有影响。在60和90 mmHg的灌注压力下，5周龄SHR的冠状动脉NOx-生成量均低于年龄匹配的WKY。15周时，SHR的血压高于WKY。SHR的冠状动脉自动调节仍高于WKY，但低于5周龄SHR。15周龄SHR的NOx-生成恢复到年龄匹配WKY的水平。这些结果表明，高血压前期5周龄SHR中机械刺激诱导的NOx-生成明显减少，这可能增强了冠状动脉自动调节。一氧化氮生成受损可能先于SHR高血压的发生。
