Influence of dual‐specificity protein phosphatase 5 on mechanical properties of rat cerebral and renal arterioles

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 Hb A1C 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. K E Y W O R D Sdistensibility, Dusp5, elastic modulus, interlobular arterioles, parenchymal arterioles, vascular stiffness

Duration and magnitude of bidirectional fluctuation in blood pressure: the link between cerebrovascular dysfunction and cognitive impairment following spinal cord injury

“…This group discovered impaired endothelial-dependent vasodilation due to loss of TRPV4 in the endothelium of cerebrovasculature in chronic SCI, together with increased vascular stiffness, contributes to cerebral hypoperfusion and cognitive deficits in chronic SCI. Cerebral parenchymal arterioles are a bottleneck of the cerebral circulation and play a major role in regulating CBF [ 9 ]. Remodeling and endothelial dysfunction of cerebral parenchymal arterioles could cause cerebral ischemic injury leading to cognitive impairment.…”

20-HETE-promoted cerebral blow flow autoregulation is associated with enhanced α-smooth muscle actin positive cerebrovascular pericyte contractility

“…Primary cerebral VSMCs were isolated from the MCA of 3-week old male SD rats, as described earlier [54][55][56][57]. Briefly, the MCAs that were dissected from the brain were placed in ice-cold Tyrode's solution, containing contained 145 mM NaCl, 6 mM KCl, 1 mM MgCl2.6H2O, 50 uM CaCl2.2H2O, 10 mM HEPES sodium salt, 4.2 mM NaHCO3, 10 mM Glucose; pH 7.4.…”

“…After incubation, the stressed matrix was detached from the wall of the plate using a sterile needle to initiate the cell contraction. Changes in the collagen gel area were measured using the equation: contraction (%) = [(Areawell -Areagel) / Areawell] X 100% and quantified with Image J software as we previously described [54][55][56][57].…”

“…A represented phase-contrast image of the vascular structure and organization of isolated vessels in the MCA territory is shown in Figure 2A. These arterioles include penetrating arterioles (when branching off from the MCA) and PAs (when entering the brain parenchyma) [57,60,62,72]. The fluid-filled Virchow-Robin space surrounding cerebral microvessels [73,74] allowed these vessels to be microdissected down to capillary levels without damaging mural cells on the vessel wall.…”

Genetic susceptibility of hypertension‐induced kidney disease

“…Sequence analysis of genes in the 2.4‐Mbp region of chromosome 1 revealed 15 known and predicted genes in the region, of which three genes (γ‐adducin ( Add3 ), dual‐specificity phosphatase 5 ( Dusp5 ), and X‐prolyl aminopeptidase 1 ( Xpnpep1 )) exhibit sequence variants in the coding regions (Burke et al., 2013). DUSP5 is a member of the threonine/tyrosine phosphatase family with the ability to specifically dephosphorylate the key molecules that regulate intracellular signal transduction, including extracellular signal‐related kinase and protein kinase C (PKC) (Kucharska et al., 2009; Owens & Keyse, 2007; Zhang et al., 2020). A study revealed that knockout (KO) of Dusp5 enhanced the myogenic response of the middle cerebral artery and autoregulation of cerebral blood flow in FHH rats (Fan et al., 2014).…”