Chamorro V, Moreno J M, Wangensteen R, Sainz J, Rodriguez-Gomez I, Osuna A, Vargas F
Departamento de Fisiología, Facultad de Medicina, Servicio de Nefrología, Unidad Experimental, Hospital Virgen de las Nieves, Granada, Spain.
J Physiol Pharmacol. 2004 Mar;55(1 Pt 1):17-26.
The role of mineralocorticoids as sodium retaining hormones has been recently enlarged to include their function as modulators of cardiovascular function and injury. This study evaluated the contribution of possible functional changes in resistance vessels to the additional BP increase produced by the chronic administration of DOCA to SHR. The flow-pressure curve and renal responses to vasoconstrictors (phenylephrine [Phe] and angiotensin II [AII]) and vasodilators (acetylcholine [ACh] and nitroprusside [NP]) were characterized in isolated kidneys from Wistar Kyoto (WKY) and SHR treated or untreated with DOCA for nine weeks. DOCA increased BP in SHR but did not modify BP in WKY rats. Kidneys from SHR showed enhanced reactivity to Phe and AII that was not increased by DOCA. DOCA reduced sensitivity to AII in SHR. Responsiveness to ACh was increased in SHR and was not attenuated by DOCA in WKY or SHR. Vasodilator response to NP was not significantly affected by DOCA in WKY or SHR. The flow-pressure curve was markedly up-shifted in SHR when compared with kidneys from WKY rats. DOCA administration did not modify the flow-pressure curve in WKY but produced attenuation at low flow levels in SHR. Our results demonstrate that DOCA increases BP in SHR but does not increase the flow-pressure curve or renal vascular reactivity to vasoconstrictors, and does not reduce responsiveness to endothelium-dependent and independent vasodilators in SHR or WKY rats. Therefore, our data suggest that the BP increase produced by DOCA in SHR is not related to abnormalities in vascular function in resistance vessels.
盐皮质激素作为保钠激素的作用最近已得到扩展，包括其作为心血管功能和损伤调节剂的功能。本研究评估了阻力血管可能的功能变化对去氧皮质酮（DOCA）长期给药导致SHR血压进一步升高的贡献。对来自Wistar Kyoto（WKY）大鼠和SHR的分离肾脏进行了血流-压力曲线以及对血管收缩剂（去氧肾上腺素[Phe]和血管紧张素II[AII]）和血管扩张剂（乙酰胆碱[ACh]和硝普钠[NP]）的肾脏反应特征分析，这些大鼠接受或未接受DOCA治疗9周。DOCA使SHR的血压升高，但对WKY大鼠的血压无影响。SHR的肾脏对Phe和AII的反应性增强，DOCA并未使其进一步增加。DOCA降低了SHR对AII的敏感性。SHR对ACh的反应性增加，在WKY或SHR中DOCA均未使其减弱。WKY或SHR中，DOCA对NP的血管扩张反应无显著影响。与WKY大鼠的肾脏相比，SHR的血流-压力曲线明显上移。给予DOCA并未改变WKY的血流-压力曲线，但使SHR在低流量水平时曲线衰减。我们的结果表明，DOCA使SHR的血压升高，但并未增加血流-压力曲线或肾脏血管对血管收缩剂的反应性，并且在SHR或WKY大鼠中并未降低对内皮依赖性和非依赖性血管扩张剂的反应性。因此，我们的数据表明，DOCA在SHR中引起的血压升高与阻力血管的血管功能异常无关。
