title: Magnolol administration in normotensive young spontaneously hypertensive rats postpones the development of hypertension: role of increased PPAR gamma, reduced TRB3 and resultant alleviative vascular insulin resistance.
abstract: Patients with prehypertension are more likely to progress to manifest hypertension than those with optimal or normal blood pressure. However, the mechanisms underlying the development from prehypertension to hypertension still remain largely elusive and the drugs for antihypertensive treatment in prehypertension are absent. Here we determined the effects of magnolol (MAG) on blood pressure and aortic vasodilatation to insulin, and investigated the underlying mechanisms. Four-week-old male spontaneous hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto (WKY) control rats were used. Our results shown that treatment of young SHRs with MAG (100 mg/kg/day, o.g.) for 3 weeks decreased blood pressure, improved insulin-induced aorta vasodilation, restored Akt and eNOS activation stimulated by insulin, and increased PPARγ and decreased TRB3 expressions. In cultured human umbilical vein endothelial cells (HUVECs), MAG incubation increased PPARγ, decreased TRB3 expressions, and restored insulin-induced phosphorylated Akt and eNOS levels and NO production, which was blocked by both PPARγ antagonist and siRNA targeting PPARγ. Improved insulin signaling in HUVECs by MAG was abolished by upregulating TRB3 expression. In conclusion, treatment of young SHRs with MAG beginning at the prehypertensive stage decreases blood pressure via improving vascular insulin resistance that is at least partly attributable to upregulated PPARγ, downregulated TRB3 and consequently increased Akt and eNOS activations in blood vessels in SHRs.
authors: Experiment Teaching Center, Fourth Military Medical University, Xi'an, China.
authors: Xiangyan
authors: X
authors: Liang
authors: Department of Physiology, Fourth Military Medical University, Xi'an, China.
authors: Wenjuan
authors: W
authors: Xing
authors: Department of Pediatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors: Jinxiao
authors: J
authors: He
authors: Department of Physiology, Fourth Military Medical University, Xi'an, China.
authors: Feng
authors: F
authors: Fu
authors: Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors: Wei
authors: W
authors: Zhang
authors: Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors: Feifei
authors: F
authors: Su
authors: Experiment Teaching Center, Fourth Military Medical University, Xi'an, China.
authors: Fange
authors: F
authors: Liu
authors: Experiment Teaching Center, Fourth Military Medical University, Xi'an, China.
authors: Lele
authors: L
authors: Ji
authors: Department of Physiology, Fourth Military Medical University, Xi'an, China.
authors: Feng
authors: F
authors: Gao
authors: Department of Geratology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors: Hui
authors: H
authors: Su
authors: Department of Pediatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors: Xin
authors: X
authors: Sun
authors: Experiment Teaching Center, Fourth Military Medical University, Xi'an, China.
authors: Haifeng
authors: H
authors: Zhang
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D001713:Biphenyl Compounds / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D003720:Densitometry; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D017705:Lignans / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D001713:Biphenyl Compounds; D007328:Insulin; D017705:Lignans; D047495:PPAR gamma; C502443:Trib3 protein, rat; C005498:magnolol; D052250:Nitric Oxide Synthase Type III; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt