Vascular Extracellular Signal-Regulated Kinase 1/2 Suppressed Perivascular Adipose Tissue-Induced Relaxation in Spontaneous Hypertensive Rats

Abstract

Background: Perivascular adipose tissue (PVAT) releases factors that regulate vascular tone (adipocyte-derived factors (ADFs) ). Mitogen-activated protein kinases (MAPKs) in blood vessels have been implicated in the development of hypertension. This study aimed to determine whether MAPKs are involved in impaired ADF-induced relaxation in hypertension.

Methods and Results: Aortic rings of Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) with or without PVAT (+PVAT rings and −PVAT rings, respectively) were placed in an organ bath filled with 5 ml of physiological salt solution (PSS). In the aortic rings of SHRs, 5-hydroxytryptamine (5-HT) -induced contraction of the −PVAT ring was increased compared with that in WKY rats. The 5-HT-induced contraction decreased in WKY rats and SHRs when PVAT was retained (+PVAT ring). After contraction with 5-HT (10^−6.5−10^−5.5 M), PSS (2 ml) was removed from the other chambers. The PSS from the +PVAT rings of WKY rats slowly relaxed the −PVAT rings; however, the PSS from the −PVAT rings of WKY rats did not. The PSS collected from the chamber with the +PVAT ring failed to relax the pre-constructed −PVAT rings of the SHR. After pretreatment of the −PVAT rings of SHR with PD98052 (20 μM: MAPK/ERK Kinase (MEK) inhibitor), the PSS from the +PVAT rings relaxed to similar degrees as in WKY rats (WKY 44%±4%, SHR −15%±8%; P<0.001 vs WKY, SHR+PD98052 45%±7%).

Conclusion: PVAT releases ADFs; however, the aorta from SHR resists relaxation with ADFs. The impairment of ADF-induced relaxation and hyperconstriction by 5-HT can be mediated by MAPKs, potentially contributing to the pathogenesis of hypertension.