Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Am J Hypertens. 2010 Mar;23(3):243-8. doi: 10.1038/ajh.2009.236. Epub 2009 Dec 3.
This study determined whether transfer of the renin gene from the Dahl salt-resistant (Dahl R) strain into the Dahl salt-sensitive (SS) genetic background restores the relaxation of middle cerebral arteries (MCAs) to different vasodilator stimuli in S/renRR renin congenic (SS.SR-(D13N1 and Syt2)/Mcwi) (RGRR) rats maintained on low-salt (0.4% NaCl) diet.
Responses to vasodilator stimuli were evaluated in isolated MCA from SS (Dahl SS/Jr/Hsd/MCWi), RGRR rats, and Dahl R rats.
MCA from SS rats failed to dilate in response to acetylcholine (ACh; 10(-6) mol/l), hypoxia (PO2 reduction to 40-45 mm Hg), and iloprost (10(-11) g/ml). ACh- and hypoxia-induced dilations were present in Dahl R rats and restored in RGRR rats. MCA from RGRR and SS constricted in response to iloprost, whereas MCA from Dahl R rats dilated in response to iloprost. MCA from SS, RGRR, and Dahl R rats exhibited similar dilations in response to cholera toxin (10(-9) g/ml) and dialated in response to the nitric oxide (NO) donor DEA-NONOate (10(-5) mol/l).
(i) Restoration of normal regulation of the renin-angiotensin system restores dilations to ACh and hypoxia that are impaired in SS rats, (ii) prostacyclin signaling is impaired in SS and RGRR rats but intact in Dahl R rats, indicating that alleles other than the renin gene affect vascular relaxation in response to this agonist; and (iii) vascular smooth muscle sensitivity to NO is preserved in SS and RGRR and is not responsible for impaired arterial relaxation in response to ACh in SS rats.
本研究旨在确定将肾素基因从达尓盐抵抗（Dahl R）品系转移到达尓盐敏感（SS）遗传背景中是否能恢复低盐（0.4% NaCl）饮食下 S/renRR 肾素同系物（SS.SR-（D13N1 和 Syt2）/Mcwi）（RGRR）大鼠大脑中动脉（MCAs）对不同血管扩张剂刺激的舒张反应。
在 SS（Dahl SS/Jr/Hsd/MCWi）、RGRR 大鼠和 Dahl R 大鼠的离体 MCA 中评估血管扩张剂刺激的反应。
SS 大鼠的 MCA 对乙酰胆碱（ACh；10(-6) mol/l）、缺氧（PO2 降至 40-45 mm Hg）和伊洛前列素（10(-11) g/ml）无舒张反应。ACh 和缺氧诱导的舒张反应存在于 Dahl R 大鼠中，并在 RGRR 大鼠中得到恢复。RGRR 和 SS 大鼠的 MCA 对伊洛前列素收缩，而 Dahl R 大鼠的 MCA 对伊洛前列素舒张。SS、RGRR 和 Dahl R 大鼠的 MCA 对霍乱毒素（10(-9) g/ml）均有相似的舒张反应，并对一氧化氮（NO）供体 DEA-NONOate（10(-5) mol/l）舒张。
（i）肾素-血管紧张素系统的正常调节的恢复恢复了 ACh 和缺氧引起的舒张反应，而 SS 大鼠的这些反应受损；（ii）SS 和 RGRR 大鼠的前列环素信号受损，但 Dahl R 大鼠的完整，表明除肾素基因以外的等位基因影响血管对该激动剂的舒张反应；（iii）SS 和 RGRR 大鼠的血管平滑肌对 NO 的敏感性得以保留，而不是 SS 大鼠对 ACh 引起的动脉舒张反应受损的原因。
