Increased Expression of Endothelin-1 and Inducible Nitric Oxide Synthase Isoform II in Aging Arteries in Vivo: Implications for Atherosclerosis

Göettsch, Winfried; Lattmann, Thomas; Amann, Kerstin; Szibor, Marten; Morawietz, Henning; Münter, Klaus; Müller, S; Shaw, Sidney; Barton, Matthias

doi:10.1006/bbrc.2000.4180

Cited by 96 publications

(65 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The increased CSE protein expression with age in aorta is similar to changes in eNOS protein expression with age in peripheral arteries, although the increase in eNOS expression is typically larger (Cernadas et al 1998;Goettsch et al 2001;van der Loo et al 2005;van der Loo et al 2000). It has been proposed that the change in eNOS is a homeostatic correction for decreased NO bioavailability or NO concentration, and that this is caused by increased superoxide reacting with NO to form a peroxynitrite (van der Loo et al 2005;van der Loo et al 2000).…”

Section: Cse and Cbs Protein Expressionmentioning

confidence: 87%

“…At higher H 2 S concentrations, sufficient H 2 S may remain to activate K ATP channels, causing the second phase relaxation (Zhao et al 2001). The concentration of NO is reduced with age (Cernadas et al 1998;Goettsch et al 2001;van der Loo et al 2005;van der Loo et al 2000), and therefore it follows that less H 2 S would be required to significantly reduce free NO in tissue of older animals. This would have the effect of increasing the apparent sensitivity of the first-phase contraction to H 2 S, consistent with our observations.…”

Section: Cse and Cbs Mrna Expressionmentioning

confidence: 99%

See 1 more Smart Citation

The hydrogen sulfide signaling system: changes during aging and the benefits of caloric restriction

Predmore

Alendy

Ahmed

et al. 2010

AGE

View full text Add to dashboard Cite

Hydrogen sulfide gas (H 2 S) is a putative signaling molecule that causes diverse effects in mammalian tissues including relaxation of blood vessels and regulation of perfusion in the liver, but the effects of aging on H 2 S signaling are unknown. Aging has negative impacts on the cardiovascular system. However, the liver is more resilient with age. Caloric restriction (CR) attenuates affects of age in many tissues. We hypothesized that the H 2 S signaling system is negatively affected by age in the vasculature but not in the liver, which is typically more resilient to age, and that a CR diet minimizes the age affect in the vasculature. To investigate this, we determined protein and mRNA expression of the H 2 S-producing enzymes cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS), H 2 S production rates in the aorta and liver, and the contractile response of aortic rings to exogenous H 2 S. Tissue was collected from Fisher 344×Brown Norway rats from 8-38 months of age, which had been maintained on an ad libitum (AL) or CR diet. The results demonstrate that age and diet have differential effects on the H 2 S signaling system in aorta and liver. The aorta showed a sizeable effect of both age and diet, whereas the liver only showed a sizeable effect of diet. Aortic rings showed increased contractile sensitivity to H 2 S and increased protein expression of CSE and CBS with age, consistent with a decrease in H 2 S concentration with age. CR appears to benefit CSE and CBS protein in both aorta and liver, potentially by reducing oxidative stress and ameliorating the negative effect of age on H 2 S concentration. Therefore, CR may help maintain the H 2 S signaling system during aging.

show abstract

Section: Cse and Cbs Protein Expressionmentioning

confidence: 87%

Section: Cse and Cbs Mrna Expressionmentioning

confidence: 99%

The hydrogen sulfide signaling system: changes during aging and the benefits of caloric restriction

Predmore

Alendy

Ahmed

et al. 2010

AGE

View full text Add to dashboard Cite

show abstract

“…29,30 We have demonstrated previously that aging activates the renal endothelin system. 13,14 This activation may be, in part, dependent on angiotensin II. 31 Indeed, early studies by Remuzzi's group have shown that inhibition of angiotensin II formation with the angiotensin-converting enzyme (ACE) inhibitor perindopril for 4 months slowed development of glomerular and tubulo-interstital injury in aging rats, effects that were accompanied by a pressure-lowering effect of the drug.…”

Section: Discussionmentioning

confidence: 99%

“…12 As we have shown previously, ET-1 expression increases in the aging kidney in the absence of other risk factors. 13,14 Because podocytes are targets of ET-1, 15 we sought to investigate the effects of treatment with an orally active ET A receptor antagonist on renal structure and function in aged rats with established glomerulosclerosis and podocyte injury.…”

mentioning

confidence: 99%

Role of Podocytes for Reversal of Glomerulosclerosis and Proteinuria in the Aging Kidney After Endothelin Inhibition

et al. 2004

Self Cite

View full text Add to dashboard Cite

Abstract-The cause of focal-segmental glomerulosclerosis as a consequence of physiological aging, which is believed to be inexorable, is unknown. This study investigated whether inhibition of endothelin-1, a growth-promoting peptide contributing to renal injury in hypertension and diabetes, affects established glomerulosclerosis and proteinuria in the aged kidney. We also determined the role of endothelin receptors for podocyte injury in vivo and in vitro. Aged Wistar rats, a model of spontaneous age-dependent glomerulosclerosis, were treated with the orally active endothelin subtype A (ET A ) receptor antagonist darusentan, and evaluation of renal histology, renal function studies, and expression analyses were performed. In vitro experiments using puromycin aminonucleoside to induce podocyte injury investigated the role of ET A receptor signaling for apoptosis, cytoskeletal injury, and DNA synthesis. In aged Wistar rats, established glomerulosclerosis and proteinuria were reduced by Ͼ50% after 4 weeks of darusentan treatment, whereas blood pressure, glomerular filtration rate, or tubulo-interstitial renal injury remained unaffected. Improvement of structural injury in glomeruli and podocytes was accompanied by a reduction of the expression of matrix metalloproteinase-9 and p21 Cip1/WAF1 . In vitro experiments blocking ET A receptors using specific antagonists or RNA interference prevented apoptosis and structural damage to podocytes induced by puromycin aminonucleoside. In conclusion, these results support the hypothesis that endogenous endothelin contributes to glomerulosclerosis and proteinuria in the aging kidney. The results further suggest that age-dependent glomerulosclerosis is not merely a "degenerative" but a reversible process locally confined to the glomerulus involving recovery of podocytes from previous injury. Key Words: arterial presure Ⅲ nephrosclerosis Ⅲ DNA Ⅲ kidney failure Ⅲ renal artery Ⅲ expression Ⅲ kidney Ⅲ renal disease A ging represents an important factor determining onset and course of disease and has become a significant issue in view of the anticipated increase of the aging population. Aging in humans and rodents progressively impairs renal function 1,2 and structure, the latter of which is characterized by damage of podocytes and mesangial matrix, as well as capillary hypertrophy and obliteration resulting in glomerulosclerosis. 2 The exact mechanisms underlying agedependent renal injury are unknown. In otherwise healthy individuals Ն65 years of age, even in the absence of known risk factors such as hypertension or diabetes, glomerulosclerosis is frequently present. 3 Currently, Ϸ1.4% of the US total population is affected, and the incidence is expected to increase to Ͼ2% within the next 15 years. 3 Glomerulosclerosis and proteinuria involve injury of podocytes, also known as glomerular epithelial cells that maintain an intact filtration barrier and control glomerular basement membrane turnover under normal conditions. 4 -7 In addition to cell-specific changes during aging, cell c...

show abstract

“…In aged spontaneously hypertensive rats there are severe renal lesions and a NO deficiency with a decrease in renal eNOS compared to young rats [21]. In the renal arteries of older rats, there is an increase in iNOS compared to what is observed in younger rats [22]. Thus, both I/R injury and aging cause alterations in the NO system in the kidney.…”

Section: Introductionmentioning

confidence: 99%

Short-term antioxidant diet prevents hyperfiltration in young male rat kidney subjected to ischemia/reperfusion injury

Slyvka¹,

Nowak²,

Hayes³

et al. 2013

OJMIP

View full text Add to dashboard Cite

Objectives: The process of transplantation is associated with exposure to both long and short cold and warm ischemic times that result in ischemia/reperfusion injury. Oxidative stress contributes to tissue fibrosis, renal dysfunction, and/or rejection. Treatments that scavenge oxygen free radicals and have antioxidant properties can ameliorate the damaging results in renal grafts following ischemia/reperfusion injury. The present study tests the hypothesis that an antioxidant-fortified diet given to rats before and after renal ischemia/reperfusion injury will reduce the kidney damage that results and improve renal function. Endothelial and inducible nitric oxide synthases may change with tissue injury, including ischemia/ reperfusion. Materials and Methods: Male Wistar rats were subjected to ischemia/reperfusion injury at 7 or 19 weeks of age with or without dietary antioxidant supplementation. One week later, glomerular filtration rate, mean arterial pressure and urinary nitric oxide were measured, and renal endothelial and inducible nitric oxide synthases examined. Results: The glomerular filtration rate was elevated more than two-fold above the normal range at 8 weeks in animals on the regular diet exposed to ischemia/reperfusion, while in the 8 week antioxidant-fortified diet group the glomerular filtration rate was normal. Also, in 8 week rats, levels of endothelial nitric oxide synthase protein in cortex were higher on the regular than on the antioxidant-fortified diet. Conclusion: Early after ischemia/reper-fusion injury renal endothelial nitric oxide synthase levels rise, possibly contributing to vascular dilation and hyperperfusion, and an antioxidant-fortified diet can ameliorate these changes in the younger age group.

show abstract

Increased Expression of Endothelin-1 and Inducible Nitric Oxide Synthase Isoform II in Aging Arteries in Vivo: Implications for Atherosclerosis

Cited by 96 publications

References 46 publications

The hydrogen sulfide signaling system: changes during aging and the benefits of caloric restriction

The hydrogen sulfide signaling system: changes during aging and the benefits of caloric restriction

Role of Podocytes for Reversal of Glomerulosclerosis and Proteinuria in the Aging Kidney After Endothelin Inhibition

Short-term antioxidant diet prevents hyperfiltration in young male rat kidney subjected to ischemia/reperfusion injury

Contact Info

Product

Resources

About