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ABSTRACT
Increased short-term blood pressure variability (BPV) is strongly correlated with target organ damage. However, the molecular mechanisms underlying abnormal BPV-induced organ damage and effective therapeutic targets are poorly understood. The purpose of this study was to investigate the effects of losartan on vasomotor function and canonical transient receptor potential (TRPC) channels in the aortas of rats with arterial pressure lability induced by sinoaortic denervation (SAD). SAD was performed in male Sprague-Dawley rats at the age of 10 weeks. The experiment included sham-operated (Sham), SAD, and losartan-treated SAD (SAD+Los) groups. After 8 weeks of treatment, hemodynamic parameters were measured via catheterization, thoracic aortic vasomotor functions were evaluated using a physiological vascular ring tension recording system, and TRPC1 and 6 mRNA and protein expression levels in the endothelial cells (ECs) and smooth muscle cells (SMCs) of the thoracic aorta were determined via reverse transcription polymerase chain reaction (RT-PCR) and Western-blotting, respectively. Compared with Sham rats, SAD rats exhibited significantly increased BPV, enhanced norepinephrine-induced aortic contraction, and attenuated acetylcholine-induced aortic relaxation. Both the mRNA and the protein expression levels of TRPC1 and 6 were significantly downregulated in the ECs and upregulated in the SMCs of the thoracic aortas of SAD rats. Losartan treatment prevented these SAD-induced changes. In conclusion, losartan efficiently prevented vasomotor function impairment in SAD rats by reducing BPV and regulating TRPC1 and 6 expression levels.
Declaration of interests
The authors report no conflicts of interest.
Funding
This research was supported by a grant from the Natural Science Foundation of Guangdong Province (NO. 2015A030313238)
Additional information
Funding
Notes on contributors
Minlie Liang
YF Liu and HC Wu designed and guided the research; ML Liang performed the main portions of the research and data analysis and prepared the manuscript; and WL Zhong and F Miao performed the other portions of the research and data collection.
Wenliang Zhong
YF Liu and HC Wu designed and guided the research; ML Liang performed the main portions of the research and data analysis and prepared the manuscript; and WL Zhong and F Miao performed the other portions of the research and data collection.
Fei Miao
YF Liu and HC Wu designed and guided the research; ML Liang performed the main portions of the research and data analysis and prepared the manuscript; and WL Zhong and F Miao performed the other portions of the research and data collection.
Hongchao Wu
YF Liu and HC Wu designed and guided the research; ML Liang performed the main portions of the research and data analysis and prepared the manuscript; and WL Zhong and F Miao performed the other portions of the research and data collection.
Yingfeng Liu
YF Liu and HC Wu designed and guided the research; ML Liang performed the main portions of the research and data analysis and prepared the manuscript; and WL Zhong and F Miao performed the other portions of the research and data collection.