PPARG Silencing Improves Blood Pressure Control and Alleviates Renal Damage by Modulating RAS Circadian Rhythm in Hypertensive Rats.

OBJECTIVE

Peroxisome proliferator-activated receptor gamma (PPARG) polymorphisms are associated with hypertension, but the role of PPARG in hypertensive nephropathy is poorly understood.

METHODS

Male Sprague-Dawley rats were applied to construct renovascular hypertension model by 2-kid-ney, 1-clip (2K1C) method. Tail vein bolus injection of adeno-associated virus (rAAV)-shPPARG was performed to knockout PPARG in 2K1C rats. The heart rate (HR), systolic pressure (SBP), diastolic pressure (DBP) and activity of rats were monitored after treatments. The role of PPARG in hypertension, renal damage, and circadian rhythm of renin-angiotensin system (RAS) was explored by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), western blot, Masson staining, hematoxylin eosin (HE) staining, Sirius red staining and enzyme-linked immunosorbent assay.

RESULTS

PPARG was over-expressed in thoracic aortas of 2K1C rats. 2K1C treatment enhanced DBP and SBP in rats, which was reversed by PPARG silencing. PPARG silencing alleviated 2K1C-induced renal damage. 2K1C treatment reduced angiotensin II and increased angiotensin converting enzyme (ACE) and plasma renin activity (PRA) concentrations in rat plasma during the light period and decreased plasma PRA concentration during the dark period, which were all overturned by PPARG silencing. PPARG silencing effectively improved the RAS circadian rhythm in hypertension.

CONCLUSION

PPARG silencing improved blood pressure control and alleviated renal damage by regulating RAS circadian rhythm in hypertensive rats.