Inhibition of heme oxygenase augments tubular sodium reabsorption

Jackson, Keith E.; Jackson, Debra; Quadri, Syed; Reitzell, Marshall J.; Navar, L. Gabriel

doi:10.1152/ajprenal.00024.2010

Cited by 17 publications

(18 citation statements)

References 37 publications

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“…Recently, we reported that HO inhibition promotes sodium and/or water retention and decreases urine flow without significant differences in haemodynamic function . However, in the present study we demonstrated changes in haemodynamic function without any differences in urine flow.…”

Section: Discussioncontrasting

confidence: 86%

Haemodynamic consequences of recurrent insulin-induced hypoglycaemia

Quadri

Prathipati

Jackson

et al. 2013

Clin Exp Pharmacol Physiol

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1. Recurring insulin-induced hypoglycaemia (RIIH) often occurs during the therapeutic management of insulin-dependent diabetes mellitus. Controversy currently exists in the literature as to the ability of insulin and/or hypoglycaemia to promote hypertension. Could insulin and/or hypoglycaemia promote adverse pressor effects? If so, under what conditions and through what mechanism? Thus, the present study was performed to evaluate the hypothesis that RIIH produces hypertension via induction of heme oxygenase (HO)-1, promoting a significant increase in endogenous carbon monoxide (CO). 2. Male Sprague-Dawley rats were treated for 2 weeks with varying doses of insulin (1, 3, 5, 7 and 9 U/kg, s.c.) or vehicle and fed normal rat chow or a zinc diet (1 mmol/L) for 2 weeks. Tail-cuff blood pressure, food intake and blood glucose states were monitored daily. 3. A dose-dependent decrease in blood glucose was observed in insulin-treated rats. Blood pressure was significantly elevated in rats treated with 9 and 7 U/kg insulin compared with those treated with other doses of insulin. However, there was no change in urine output among the groups. Feeding of a high-zinc diet to rats treated with 7 U/kg insulin and treatment with the HO-1 inhibitor zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG; 20 mg/kg) after insulin injection resulted in a significant reduction in blood pressure compared with 7 U/kg insulin injection alone. In addition, HO-1 protein levels in the heart and kidney and endogenous CO levels were reduced in 7 U/kg insulin-treated rats fed the high-zinc diet compared with those treated with the same dose of insulin alone. 4. The results of the present study demonstrate that RIIH promotes hypertension and that restoration of normal CO levels with a high-zinc diet and ZnDPBG reduces blood pressure.

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Section: Discussioncontrasting

confidence: 86%

Haemodynamic consequences of recurrent insulin-induced hypoglycaemia

Quadri

Prathipati

Jackson

et al. 2013

Clin Exp Pharmacol Physiol

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“…The HO inhibitor chromium mesoporphyrin decreased renal HO-1 and CO but did not affect RBF or GFR or NO production in the rat (718). In another study, HO inhibition increased RVR in the rat kidney which was more pronounced when NOS was inhibited (1242).…”

Section: Carbon Monoxidementioning

confidence: 88%

Renal Autoregulation in Health and Disease

Carlström

Wilcox

Arendshorst

2015

Physiological Reviews

375

383

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Intrarenal autoregulatory mechanisms maintain renal blood flow (RBF) and glomerular filtration rate (GFR) independent of renal perfusion pressure (RPP) over a defined range (80-180 mmHg). Such autoregulation is mediated largely by the myogenic and the macula densa-tubuloglomerular feedback (MD-TGF) responses that regulate preglomerular vasomotor tone primarily of the afferent arteriole. Differences in response times allow separation of these mechanisms in the time and frequency domains. Mechanotransduction initiating the myogenic response requires a sensing mechanism activated by stretch of vascular smooth muscle cells (VSMCs) and coupled to intracellular signaling pathways eliciting plasma membrane depolarization and a rise in cytosolic free calcium concentration ([Ca(2+)]i). Proposed mechanosensors include epithelial sodium channels (ENaC), integrins, and/or transient receptor potential (TRP) channels. Increased [Ca(2+)]i occurs predominantly by Ca(2+) influx through L-type voltage-operated Ca(2+) channels (VOCC). Increased [Ca(2+)]i activates inositol trisphosphate receptors (IP3R) and ryanodine receptors (RyR) to mobilize Ca(2+) from sarcoplasmic reticular stores. Myogenic vasoconstriction is sustained by increased Ca(2+) sensitivity, mediated by protein kinase C and Rho/Rho-kinase that favors a positive balance between myosin light-chain kinase and phosphatase. Increased RPP activates MD-TGF by transducing a signal of epithelial MD salt reabsorption to adjust afferent arteriolar vasoconstriction. A combination of vascular and tubular mechanisms, novel to the kidney, provides for high autoregulatory efficiency that maintains RBF and GFR, stabilizes sodium excretion, and buffers transmission of RPP to sensitive glomerular capillaries, thereby protecting against hypertensive barotrauma. A unique aspect of the myogenic response in the renal vasculature is modulation of its strength and speed by the MD-TGF and by a connecting tubule glomerular feedback (CT-GF) mechanism. Reactive oxygen species and nitric oxide are modulators of myogenic and MD-TGF mechanisms. Attenuated renal autoregulation contributes to renal damage in many, but not all, models of renal, diabetic, and hypertensive diseases. This review provides a summary of our current knowledge regarding underlying mechanisms enabling renal autoregulation in health and disease and methods used for its study.

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“…Changes in renal cortical and medullary blood flow were determined by laser flowmeter (Advance Laser Flowmeter ALF 21D, Tokyo, Japan) as described earlier [16–17]. Glomerular filtration rate (GFR) was measured based on inulin clearance as previously described [18–19].…”

Section: Methodsmentioning

confidence: 99%

(Pro)renin receptor contributes to regulation of renal epithelial sodium channel

Quadri

Siragy

2016

Journal of Hypertension

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Recent studies reported increased (Pro)renin receptor (PRR) expression during low-salt intake. We hypothesized that PRR plays a role in regulation of renal epithelial sodium channel (ENaC) through serum and glucocorticoid-inducible kinase isoform 1 (SGK-1)-neural precursor cell expressed, developmentally downregulated 4–2 (Nedd4–2) signaling pathway. Male Sprague–Dawley rats on normal-sodium diet and mouse renal inner medullary collecting duct cells treated with NaCl at 130 mmol/l (normal salt), or 63 mmol/l (low salt) were studied. PRR and α-ENaC expressions were evaluated 1 week after right uninephrectomy and left renal interstitial administration of 5% dextrose, scramble shRNA, or PRR shRNA (n = 6 each treatment). In-vivo PRR shRNA significantly reduced expressions of PRR throughout the kidney and α-ENaC subunits in the renal medulla. In inner medullary collecting duct cells, low salt or angiopoietin II (Ang II) augmented the mRNA and protein expressions of PRR (P < 0.05), SGK-1 (P < 0.05), and α-ENaC (P < 0.05). Low salt or Ang II increased the phosphorylation of Nedd4–2. In cells treated with low salt or Ang II, PRR siRNA significantly downregulated the mRNA and protein expressions of PRR (P < 0.05), SGK-1 (P < 0.05), and α-ENaC expression (P < 0.05). We conclude that PRR contributes to the regulation of α-ENaC via SGK-1-Nedd4–2 signaling pathway.

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Inhibition of heme oxygenase augments tubular sodium reabsorption

Cited by 17 publications

References 37 publications

Haemodynamic consequences of recurrent insulin-induced hypoglycaemia

Haemodynamic consequences of recurrent insulin-induced hypoglycaemia

Renal Autoregulation in Health and Disease

(Pro)renin receptor contributes to regulation of renal epithelial sodium channel

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