Role of 20-HETE in the antihypertensive effect of transfer of chromosome 5 from Brown Norway to Dahl salt-sensitive rats

Williams, Jan Michael; Fan, Fan; Murphy, Sydney; Schreck, Carlos; Lazar, Jozef; Jacob, Howard J.; Roman, Richard J.

doi:10.1152/ajpregu.00604.2011

Cited by 47 publications

(65 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The role of 20-HETE in the impairment of Af-Art myogenic response in Dahl SS rats is unknown, but Dahl SS rats are known to have a decreased 20-HETE production in renal microvessels (32). Thus, we hypothesize that a decrease in 20-HETE in Dahl SS rats causes an impairment in myogenic response and ATP-induced Af-Art constriction.…”

mentioning

confidence: 89%

Mechanism of impaired afferent arteriole myogenic response in Dahl salt-sensitive rats: role of 20-HETE

Ren

D’Ambrosio

Garvin

et al. 2014

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

The afferent arteriole (Af-Art) controls glomerular capillary pressure, an important determinant of glomerular injury. Af-Art myogenic response is mediated by ATP, and ATP signaling is in turn mediated by 20-HETE. Dahl salt-sensitive rats (Dahl SS) have decreased renal 20-HETE production. We hypothesized that Dahl SS have an impaired myogenic response and constrictor response to ATP, due to decreased 20-HETE. Af-Arts from Dahl SS or Dahl salt-resistant rats (Dahl SR) were microdissected and perfused. When myogenic response was induced by increasing Af-Art perfusion pressure from 60 to 140 mmHg, luminal Af-Art diameter decreased in Dahl SR but not in Dahl SS (-3.1 ± 0.8 vs. 0.5 ± 0.8 μm, P < 0.01). The 20-HETE antagonist 20-HEDE (10(-6) M) blocked the myogenic response in Dahl SR but had no effect in Dahl SS. Addition of a subconstrictor concentration of 20-HETE (but not a subconstrictor concentration of norepinephrine) restored the myogenic response in Dahl SS. We then perfused Af-Arts at 60 mmHg and tested the effects of the ATP analog α,β-methylene-ATP (10(-6) M). Maximum ATP-induced constriction was attenuated in Dahl SS compared with Dahl SR (1.5 ± 0.5 vs. 7.4 ± 0.8 μm, P < 0.001). 20-HEDE attenuated ATP-induced Af-Art constriction in Dahl SR but not in Dahl SS, and consequently, ATP-induced constriction was no longer different between strains. In conclusion, Dahl SS have an impaired myogenic response and ATP-induced Af-Art constriction due to a decrease in Af-Art 20-HETE. The impaired myogenic responses may contribute to the nephrosclerosis that develops in Dahl SS.

show abstract

mentioning

confidence: 89%

Mechanism of impaired afferent arteriole myogenic response in Dahl salt-sensitive rats: role of 20-HETE

Ren

D’Ambrosio

Garvin

et al. 2014

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

show abstract

“…When 20-HETE synthesis is suppressed in a cerebral infarction rat model, infarct size can be reduced (Imaoka et al, 2005). In a hypertensive rat model, the increased 20-HETE production can lead to oxidative stress and endothelial cell damage, resulting in increased incidence of IS (Williams et al, 2012). CYP4F2 is the major synthase that catalyzes arachidonic acid to generate 20-HETE.…”

Section: Introductionmentioning

confidence: 99%

CYP4F2 gene single nucleotide polymorphism is associated with ischemic stroke

Yuan¹,

Zhang²,

Huang³

et al. 2015

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. The objective of this study was to explore the relationship between CYP4F2 gene polymorphism and ischemic stroke (IS) in the Han Chinese population. We performed a case-control study to genotype four single nucleotide polymorphisms (SNPs) (rs2108622, rs3093100, rs3093105, rs3093135) in the CYF4F2 gene. The genotype and haplotype distributions were compared between the case and control groups. We found that the GG genotype of rs2108622 in the CYP4F2 gene was associated with risk of IS (P = 0.023). Haplotype analysis indicated that the GGGT haplotype comprising rs2108622-rs3093100-rs3093105-rs3093135 was associated with IS, which suggests that the GGGT haplotype may be a risk factor for IS (P = 0.012). CYP4F2 gene polymorphism might increase the risk of IS in the Chinese population.

show abstract

“…10,11 Basal levels of 20-HETE in the cortex and renal medulla were significantly higher in the SS. Figure 8.…”

Section: Comparison Of 20-hete Levels and Susceptibility Tomentioning

confidence: 96%

“…Our group has reported that the genes encoding the CYP4A enzymes that catalyze the renal formation of 20-HETE are located on chromosome 5 in the rat 17 and that the expression of CYP4A enzymes and the formation of 20-HETE are reduced in SS rats relative to other strains. 10,11 More recently, we found that administration of a 20-HETE agonist can protect the kidney from IR injury. 18 This was associated with prevention of the secondary fall in medullary blood flow (MBF) and prolonged tissue hypoxia that developed 2 hours after reperfusion.…”

mentioning

confidence: 97%

See 1 more Smart Citation

Deficiency in the Formation of 20-Hydroxyeicosatetraenoic Acid Enhances Renal Ischemia-Reperfusion Injury

Muroya¹,

Fan²,

Regner

et al. 2015

Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

Ischemia-reperfusion (IR) injury is the most common cause of AKI. The susceptibility to develop AKI varies widely among patients. However, little is known about the genes involved. 20-Hydroxyeicosatetraenoic acid (20-HETE) has an important role in the regulation of renal tubular and vascular function and has been implicated in IR injury. In this study, we examined whether a deficiency in the renal formation of 20-HETE enhances the susceptibility of Dahl salt-sensitive (SS) rats to ischemic AKI. Transfer of chromosome 5 containing the CYP4A genes responsible for the formation of 20-HETE from the Brown Norway (BN) rat onto the SS genetic background increased renal 20-HETE levels after ischemia and reduced plasma creatinine levels (6SEM) 24 hours after IR from 3.760.1 to 2.060.2 mg/dl in an SS.5 BN -consomic strain.Transfer of this chromosome also prevented the secondary decline in medullary blood flow and ischemia that develops 2 hours after IR in the susceptible SS strain. Blockade of the synthesis of 20-HETE with HET0016 reversed the renoprotective effects in SS.5 BN rats. Similar results were observed in an SS.5 Lewcongenic strain, in which a smaller region of chromosome 5 containing the CYP4A genes from a Lewis rat was introgressed onto the SS genetic background. These results indicate that 20-HETE has a protective role in renal IR injury by maintaining medullary blood flow and that a genetic deficiency in the formation of 20-HETE increases the susceptibility of SS rats to ischemic AKI. AKI is a common condition that is associated with significant mortality. 1 The incidence of AKI has increased by 10% per year over the last decade, and the mortality rate has more than doubled. 2 Renal ischemia-reperfusion (IR) injury is the most frequent cause of AKI, and the incidence of AKI exceeds 50% after major cardiac, aortic, or transplant surgery. 3,4 Unfortunately, there is no approved therapy for the treatment of AKI. 5 The susceptibility to develop AKI also varies widely among patients 6 and among different strains of rats. In this regard, Basile et al. 7,8 previously reported that Brown Norway (BN) rats are more resistant to the development of IR injury than Sprague-Dawley or Dahl salt-sensitive (SS) rats.More recently, transfer of the X chromosome and chromosomes 3-8, 10, and 15 from BN rats has been reported to confer partial protection to renal IR injury in consomic strains of SS rats. 8 However, little is known about the genes or mechanisms involved. Previous studies have indicated that 20-hydroxyeicosatetraenoic acid (20-HETE) plays an important role in the regulation of renal tubular and vascular

show abstract

Role of 20-HETE in the antihypertensive effect of transfer of chromosome 5 from Brown Norway to Dahl salt-sensitive rats

Cited by 47 publications

References 43 publications

Mechanism of impaired afferent arteriole myogenic response in Dahl salt-sensitive rats: role of 20-HETE

Mechanism of impaired afferent arteriole myogenic response in Dahl salt-sensitive rats: role of 20-HETE

CYP4F2 gene single nucleotide polymorphism is associated with ischemic stroke

Deficiency in the Formation of 20-Hydroxyeicosatetraenoic Acid Enhances Renal Ischemia-Reperfusion Injury

Contact Info

Product

Resources

About