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

• Published in: PloS one Vol. 10; no. 3; p. e0120366
• Main Authors: Liang, Xiangyan, Xing, Wenjuan, He, Jinxiao, Fu, Feng, Zhang, Wei, Su, Feifei, Liu, Fange, Ji, Lele, Gao, Feng, Su, Hui, Sun, Xin, Zhang, Haifeng
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.03.2015; Public Library of Science (PLoS)
• Subjects: AKT protein; Animals; Antihypertensives; Aorta; Aorta - drug effects; Aorta - physiopathology; Biphenyl Compounds - administration & dosage; Biphenyl Compounds - pharmacology; Biphenyl Compounds - therapeutic use; Blood; Blood pressure; Blood Pressure - drug effects; Blood vessels; Blood Vessels - drug effects; Blood Vessels - pathology; Blood Vessels - physiopathology; Densitometry; Drug development; Drugs; Endothelial cells; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Hypertension; Hypertension - drug therapy; Hypertension - physiopathology; Insulin; Insulin - pharmacology; Insulin Resistance; Kinases; Lignans - administration & dosage; Lignans - pharmacology; Lignans - therapeutic use; Nitric oxide; Nitric Oxide Synthase Type III - metabolism; Peroxisome proliferator-activated receptors; PPAR gamma - antagonists & inhibitors; PPAR gamma - metabolism; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Rodents; Signal Transduction - drug effects; Signaling; siRNA; Umbilical vein; Up-Regulation - drug effects; Vasodilation; Vasodilation - drug effects; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0120366

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.