Abstract
We recently reported that KO of Dual‐specificity protein phosphatase 5 (Dusp5) enhances myogenic reactivity and blood flow autoregulation in the cerebral and renal circulations in association with increased levels of pPKC and pERK1/2 in the cerebral and renal arteries and arterioles. In the kidney, hypertension‐related renal damage was significantly attenuated in Dusp5 KO rats. Elevations in pPKC and pERK1/2 promote calcium influx in VSMC and facilitate vasoconstriction. However, whether DUSP5 plays a role in altering the passive mechanical properties of cerebral and renal arterioles has never been investigated. In this study, we found that KO of Dusp5 did not alter body weights, kidney and brain weights, plasma glucose, and HbA1C levels. The expression of pERK is higher in the nucleus of primary VSMC isolated from Dusp5 KO rats. Dusp5 KO rats exhibited eutrophic vascular hypotrophy with smaller intracerebral parenchymal arterioles and renal interlobular arterioles without changing the wall‐to‐lumen ratios. These arterioles from Dusp5 KO rats displayed higher myogenic tones, better distensibility, greater compliance, and less stiffness compared with arterioles from WT control rats. VSMC of Dusp5 KO rats exhibited a stronger contractile capability. These results demonstrate, for the first time, that DUSP5 contributes to the regulation of the passive mechanical properties of cerebral and renal arterioles and provide new insights into the role of DUSP5 in vascular function, cancer, stroke, and other cardiovascular diseases.
Highlights
Dual-specificity protein phosphatase 5 (DUSP5) inactivates the extracellular signal-related kinase (ERK1/2) by dephosphorylating threonine/tyrosine residues (Alonso et al, 2004; Kidger & Keyse, 2016; Tonks, 2013)
This study investigated the possible role of DUSP5 on vascular mechanical properties by comparing the sizes, incremental distensibility, circumferential wall strain, stress, and the elastic modulus of the intracerebral parenchymal arterioles (PAs) and renal interlobular arterioles (IAs) isolated from Dual-specificity protein phosphatase 5 (Dusp5) KO and WT rats
Intact cerebral PAs and renal IAs isolated from Dusp5 KO and WT rats were mounted on glass cannulas in a pressure myography chamber (Living System Instrumentation) mounted on an IMT-2 inverted microscope (Olympus)
Summary
Dual-specificity protein phosphatase 5 (DUSP5) inactivates the extracellular signal-related kinase (ERK1/2) by dephosphorylating threonine/tyrosine residues (Alonso et al, 2004; Kidger & Keyse, 2016; Tonks, 2013). We previously reported that knockout (KO) of Dusp enhances myogenic reactivity and blood flow autoregulation in the cerebral and renal circulations, which is associated with increased levels of phosphorylated protein kinase C (pPKC) and ERK1/2 (pERK1/2) in the cerebral and renal arteries and arterioles (Fan et al, 2014; Zhang et al, 2019). The afferent arterioles (Afarts), middle cerebral arteries (MCAs), and renal interlobular arterioles (IAs) of Dusp KO rats exhibited enhanced constrictions in response to elevated transmural pressure, we found these vessels are not larger in calcium-free media compared with those isolated from wild-type (WT) control rats (Fan et al, 2014; Zhang et al, 2019).
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