Cystathione gamma lyase/Hydrogen Sulphide Pathway Up Regulation Enhances the Responsiveness of α1A and α1B-Adrenoreceptors in the Kidney of Rats with Left Ventricular Hypertrophy

Asghari, Ahmad; Sattar, M. A.; Azam, Maleeha; Abdulla, Mohammed H.; Khan, Shamsuddin Sultan; Hashmi, Furqan K.; Abdullah, Nor Azizan; Johns, Edward J.

doi:10.1371/journal.pone.0154995

Cited by 6 publications

(4 citation statements)

References 64 publications

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“…The findings from the present study adds further credence that Hhcy and low levels of H 2 S contribute to hypertension and renal pathology and supplementation of H 2 S reduces systolic blood pressure. Further, exogenous H 2 S supplementation is reported to increase CSE activity, which may therefore reduce plasma Hcy levels as observed in our study 28 .…”

Section: Discussionsupporting

confidence: 72%

Hydrogen Sulfide Protects Hyperhomocysteinemia-Induced Renal Damage by Modulation of Caveolin and eNOS Interaction

Pushpakumar

Kundu

Sen

2019

Sci Rep

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The accumulation of homocysteine (Hcy) during chronic kidney failure (CKD) can exert toxic effects on the glomeruli and tubulo-interstitial region. Among the potential mechanisms, the formation of highly reactive metabolite, Hcy thiolactone, is known to modify proteins by N-homocysteinylation, leading to protein degradation, stress and impaired function. Previous studies documented impaired nitric oxide production and altered caveolin expression in hyperhomocysteinemia (HHcy), leading to endothelial dysfunction. The aim of this study was to determine whether Hhcy homocysteinylates endothelial nitric oxide synthase (eNOS) and alters caveolin-1 expression to decrease nitric oxide bioavailability, causing hypertension and renal dysfunction. We also examined whether hydrogen sulfide (H2S) could dehomocysteinylate eNOS to protect the kidney. WT and Cystathionine β-Synthase deficient (CBS+/−) mice representing HHcy were treated without or with sodium hydrogen sulfide (NaHS), a H2S donor (30 µM), in drinking water for 8 weeks. Hhcy mice (CBS+/−) showed low levels of plasma H2S, elevated systolic blood pressure (SBP) and renal dysfunction. H2S treatment reduced SBP and improved renal function. Hhcy was associated with homocysteinylation of eNOS, reduced enzyme activity and upregulation of caveolin-1 expression. Further, Hhcy increased extracellular matrix (ECM) protein deposition and disruption of gap junction proteins, connexins. H2S treatment reversed the changes above and transfection of triple genes producing H2S (CBS, CSE and 3MST) showed reduction of vascular smooth muscle cell proliferation. We conclude that during Hhcy, homocysteinylation of eNOS and disruption of caveolin-mediated regulation leads to ECM remodeling and hypertension, and H2S treatment attenuates renovascular damage.

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Section: Discussionsupporting

confidence: 72%

Hydrogen Sulfide Protects Hyperhomocysteinemia-Induced Renal Damage by Modulation of Caveolin and eNOS Interaction

Pushpakumar

Kundu

Sen

2019

Sci Rep

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“…NaHS was administered i.p. at a dose of 56 µmol/kg daily for a period of 35 days [40,41]. Stock solution of NaHS was prepared daily by dissolving NaHS in normal saline (0.9% w/v).…”

Section: Exogenous Administration Of Nahsmentioning

confidence: 99%

“…Histopathology of kidney tissue followed a previously reported procedure [41]. Briefly, kidneys of all groups of WKY and L-NAME rats undergoing ischemia-reperfusion injury were extracted at the end of the experiments and placed in the 10% formalin.…”

Section: Histopathology Of Rat Kidney Tissues Of Wky and L-name Groupsmentioning

confidence: 99%

Hydrogen Sulphide Treatment Prevents Renal Ischemia-Reperfusion Injury by Inhibiting the Expression of ICAM-1 and NF-kB Concentration in Normotensive and Hypertensive Rats

et al. 2021

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Our main objective was to investigate the effect of chronic administration of hydrogen sulphide donor (sodium hydrosulphide) on the expression of intercellular adhesion molecule-1 (ICAM-1) and concentration of nuclear factor-kappa B (NF-kB) in a renal ischemia-reperfusion injury (IRI) model of WKY and L-nitro-arginine-methyl-ester (L-NAME)-induced hypertensive rats. Sodium hydrosulphide (NaHS) was administered intraperitoneally (i.p.) for 35 days while cystathionine gamma lyase (CSE) inhibitor dL-propargylglycine (PAG) was administered at a single dose of 50 mg/kg. Animals were anesthetised using sodium pentobarbitone (60 mg/kg) and then prepared to induce renal ischemia by clamping the left renal artery for 30 min followed by 3 h of reperfusion. Pre-treatment with NaHS improved the renal functional parameters in both WKY and L-NAME-induced hypertensive rats along with reduction of blood pressure in hypertensive groups. Oxidative stress markers like malondialdehyde (MDA), total superoxide dismutase (T-SOD) and glutathione (GSH) were also improved by NaHS treatment following renal IRI. Levels of ICAM-1 and NF-kB concentration were reduced by chronic treatment with NaHS and increased by PAG administration after renal IRI in plasma and kidney. Treatment with NaHS improved tubular morphology and glomerulus hypertrophy. Pre-treatment with NaHS reduced the degree of renal IRI by potentiating its antioxidant and anti-inflammatory mechanism, as evidenced by decreased NF-kB concentration and downregulation of ICAM-1 expression.

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“…Different doses of NA, PE and ME were administered intrarenally in ascending and descending order as described below; NA at 25, 50, 100 and 200ng; PE at 0.25, 0.5,1 and 2μg; ME at 1, 2, 3 and 4 μg. These drugs were prepared in saline (0.9g of NaCl/L of water) freshly every day and stored in 4°C [ 42 , 46 ]. A wash out time of 10 min was given to each dose administered to ensure washout of agonists [ 47 , 48 ].…”

Section: Methodsmentioning

confidence: 99%

Interaction between nitric oxide and renal α1-adrenoreceptors mediated vasoconstriction in rats with left ventricular hypertrophyin Wistar Kyoto rats

et al. 2018

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Left ventricular hypertrophy (LVH) is associated with decreased responsiveness of renal α1-adrenoreceptors subtypes to adrenergic agonists. Nitric oxide donors are known to have antihypertrophic effects however their impact on responsiveness of renal α1-adrenoreceptors subtypes is unknown. This study investigated the impact of nitric oxide (NO) and its potential interaction with the responsiveness of renal α1-adrenoreceptors subtypes to adrenergic stimulation in rats with left ventricular hypertrophy (LVH). This study also explored the impact of NO donor on CSE expression in normal and LVH kidney. LVH was induced using isoprenaline and caffeine in drinking water for 2 weeks while NO donor (L-arginine, 1.25g/Lin drinking water) was given for 5 weeks. Intrarenal noradrenaline, phenylephrine and methoxamine responses were determined in the absence and presence of selective α1-adrenoceptor antagonists, 5- methylurapidil (5-MeU), chloroethylclonidine (CeC) and BMY 7378. Renal cortical endothelial nitric oxide synthase mRNA was upregulated 7 fold while that of cystathione γ lyase was unaltered in the NO treated LVH rats (LVH-NO) group compared to LVH group. The responsiveness of renal α1A, α1B and α1D-adrenoceptors in the low dose and high dose phases of 5-MeU, CEC and BMY7378 to adrenergic agonists was increased along with cGMP in the kidney of LVH-NO group. These findings suggest that exogenous NO precursor up-regulated the renal eNOS/NO/cGMP pathway in LVH rats and resulted in augmented α1A, α1B and α1D adrenoreceptors responsiveness to the adrenergic agonists. There is a positive interaction between H2S and NO production in normal animals but this interaction appears absent in LVH animals.

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Cystathione gamma lyase/Hydrogen Sulphide Pathway Up Regulation Enhances the Responsiveness of α1A and α1B-Adrenoreceptors in the Kidney of Rats with Left Ventricular Hypertrophy

Cited by 6 publications

References 64 publications

Hydrogen Sulfide Protects Hyperhomocysteinemia-Induced Renal Damage by Modulation of Caveolin and eNOS Interaction

Hydrogen Sulfide Protects Hyperhomocysteinemia-Induced Renal Damage by Modulation of Caveolin and eNOS Interaction

Hydrogen Sulphide Treatment Prevents Renal Ischemia-Reperfusion Injury by Inhibiting the Expression of ICAM-1 and NF-kB Concentration in Normotensive and Hypertensive Rats

Interaction between nitric oxide and renal α1-adrenoreceptors mediated vasoconstriction in rats with left ventricular hypertrophyin Wistar Kyoto rats

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