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Atorvastatin attenuates vascular remodelling in spontaneously hypertensive rats via the protein kinase D/extracellular signal‐regulated kinase 5 pathway
Author(s) -
Yuan Haitao,
Wang Deyu,
Zhang Yuying,
Geng Jing
Publication year - 2020
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.13319
Subject(s) - atorvastatin , sirius red , endocrinology , medicine , vascular remodelling in the embryo , hydroxyproline , spontaneously hypertensive rat , blood pressure , protein kinase a , kinase , chemistry , fibrosis , biochemistry
The present study was conducted to determine whether atorvastatin reduces hypertension‐induced vascular remodelling and whether its effects involve protein kinase D (PKD) and extracellular signal‐regulated kinase 5 (ERK5). We used 16‐week‐old spontaneously hypertensive rats (SHRs) and age‐matched Wistar‐Kyoto (WKY) rats. The blood pressure and serum lipid concentration were measured. Changes in the vascular morphology and histology were examined using H&E, Masson ’ s trichrome, and Sirius Red staining. The media thickness (MT), ratio of MT to lumen diameter (LD) (MT/LD), collagen volume fraction (CVF) and hydroxyproline content were measured to evaluate vascular remodelling. Atorvastatin (50 mg/kg/day) was administered for 8 weeks. Increased blood pressure and vascular remodelling were more prominent in SHRs than in WKY rats. SHRs also had elevated PKD and ERK5 activation. The systolic blood pressure, MT/LD ratio, and hydroxyproline content were positively correlated with the activation level of PKD and ERK5 in SHRs. Atorvastatin significantly attenuated the activation of PKD and ERK5. Overall, this study demonstrated that atorvastatin could reverse vascular remodelling in SHRs. The PKD/ERK5 signalling pathway might be important for elucidating the beneficial pleiotropic effects of atorvastatin on vascular remodelling.