Role of COX-2 in the Enhanced Vasoconstrictor Effect of Arachidonic Acid in the Diabetic Rat Kidney

Chen, Yu-Jung

doi:10.1161/01.hyp.0000085650.29823.f2

Cited by 52 publications

(52 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Harris' group reported that chronic administration of a COX-2 inhibitor to hypertensive diabetic rats reduced the appearance of markers for renal damage, suggesting that increased COX-2 may be an early step in the development of nephropathy (Cheng et al, 2002). We confirmed the increase in the renal cortical expression of COX-2 in untreated STZ-diabetic rats and showed that a COX-2 inhibitor reduced the enhanced endoperoxide-mediated renal vasoconstrictor response to AA as well as the enhanced associated release of prostaglandins that we had reported for the diabetic rat (Quilley and McGiff, 1990;Quilley and Chen, 2003).…”

supporting

confidence: 86%

Effect of Tempol on Renal Cyclooxygenase Expression and Activity in Experimental Diabetes in the Rat

Chen²,

Quilley³

2005

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

Renal cyclooxygenase (COX)-2 expression is increased in the streptozotocin (STZ)-diabetic rat and is associated with enhanced renal prostaglandin release in response to arachidonic acid (AA). Endoperoxide-mediated vasoconstrictor responses to AA were also enhanced in the diabetic rat kidney. Because oxidative stress is increased in diabetes and has been shown to induce COX-2, we assessed its contribution to prostaglandin release by treating diabetic rats with tempol (120 mg/kg/day) for 28 days. Release of AA-stimulated prostaglandins PGE 2 and 6-ketoPGF 1␣ from the isolated perfused kidney was used as an index of COX activity, and Western analysis was used to determine COX-2 protein expression. In untreated diabetic rats, the release of prostaglandins in response to AA was markedly enhanced; the increase in release of both 6-ketoPGF 1␣ and PGE 2 after AA was twice that in control rats. Renal cortical COX-2 expression in diabetic rats was 3-fold that of control rats. Tempol treatment reduced the AA-stimulated release of prostaglandins to levels seen in control rats; this was associated with reduced expression of COX-2 protein to levels not different from that in control rats. However, the enhanced vasoconstrictor response to AA in diabetic rats was unaffected by tempol treatment but abolished by inhibition of COX-1 with SC58560 [5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole]. The addition of tempol to the perfusate of kidneys from diabetic and control rats had only a slight effect on prostaglandin release. We conclude that oxidative stress is an integral component of the mechanism involved in the induction of renal COX-2 in diabetes.

show abstract

supporting

confidence: 86%

Effect of Tempol on Renal Cyclooxygenase Expression and Activity in Experimental Diabetes in the Rat

Chen²,

Quilley³

2005

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

show abstract

“…This model allows the accurate control of regional hemodynamic variables such as perfusion pressure and flow intensity, as well as the elimination of neurohumoral and blood cell influences on renal function. Actually, the model of the isolated kidney perfused at constant flow with salt solutions has been demonstrated to be a valuable tool for the study of the regulation of renal vascular tone (2,42,52,57). Using this experimental setup, we demonstrated for the first time that exercise training of moderate intensity increases vasodilation of whole renal circulation elicited by endothelium-dependent and -independent vasodilating agents.…”

Section: Exercise Training and Renal Vascular Reactivitymentioning

confidence: 96%

Effects of exercise training on the vascular reactivity of the whole kidney circulation in rabbits

Moraes¹,

Gioseffi²,

Nóbrega³

et al. 2004

Journal of Applied Physiology

View full text Add to dashboard Cite

is known to improve vasodilating mechanisms mediated by endothelium-dependent relaxing factors in the cardiac and skeletal muscle vascular beds. However, the effects of exercise training on visceral vascular reactivity, including the renal circulation, are still unclear. We used the experimental model of the isolated perfused rabbit kidney, which involves both the renal macro-and microcirculation, to test the hypothesis that exercise training improves vasodilator mechanisms in the entire renal circulation. New Zealand White rabbits were pen confined (Sed; n ϭ 24) or treadmill trained (0% grade) for 5 days/wk at a speed of 18 m/min during 60 min over a 12-wk period (ExT; n ϭ 24). Kidneys isolated from Sed and ExT rabbits were continuously perfused in a nonrecirculating system under conditions of constant flow and precontracted with norepinephrine (NE). We assessed the effects of exercise training on renal vascular reactivity using endothelial-dependent [acetylcholine (ACh) and bradykinin (BK)] and -independent [sodium nitroprusside (SNP)] vasodilators. ACh induced marked and dose-related vasodilator responses in kidneys from Sed rabbits, the reduction in perfusion pressure reaching 41 Ϯ 8% (n ϭ 6; P Ͻ 0.05). In the kidneys from ExT rabbits, vasodilation induced by ACh was significantly enhanced to 54 Ϯ 6% (n ϭ 6; P Ͻ 0.05). In contrast, BK-induced renal vasodilation was not enhanced by training [19 Ϯ 8 and 13 Ϯ 4% reduction in perfusion pressure for Sed and ExT rabbits, respectively (n ϭ 6; P Ͼ 0.05)]. Continuous perfusion of isolated kidneys from ExT animals with N -nitro-L-arginine methyl ester (L-NAME; 300 M), an inhibitor of nitric oxide (NO) biosynthesis, completely blunted the additional vasodilation elicited by ACh [reduction in perfusion pressure of 54 Ϯ 6 and 38 Ϯ 5% for ExT and L-NAME ϩ ExT, respectively (n ϭ 6; P Ͻ 0.05)]. On the other hand, L-NAME infusion did not affect ACh-induced vasodilation in Sed animals. Exercise training also increased renal vasodilation induced by SNP [36 Ϯ 7 and 45 Ϯ 10% reduction in perfusion pressure for Sed and ExT rabbits, respectively (n ϭ 6; P Ͻ 0.05)]. It is concluded that exercise training alters the rabbit kidney vascular reactivity, enhancing endothelium-dependent and -independent renal vasodilation. This effect seems to be related not only to an increased bioavailability of NO but also to the enhanced responsiveness of the renal vascular smooth muscle to NO. chronic exercise; endothelial dysfunction; isolated perfused rabbit kidney IT IS WELL KNOWN THAT THE endothelium plays a role of paramount importance in the regulation of the vasomotor tone (for review, see Ref. 26). The endothelial cells synthesize and release several relaxing and contracting diffusible substances that interact with the underlying vascular smooth muscle, thus contributing to the continuous modulation of vascular reactivity (26). The best-characterized endothelium-derived relaxing factors are nitric oxide (NO) and prostacyclin (PGI 2 ), which can be released by physical (shear stress by the fl...

show abstract

“…Hyperglycemia-induced ROS production (in the mitochondria) occurs in endothelial cells and in platelets through auto-oxidation of glucose [Wolff and Dean, 1987], advanced glycation end (AGE) product formation and the binding of AGEs to their receptors [Yan et al, 1994;Ceriello, 1999], increased substrate flux through the polyol pathway [Giugliano et al, 1996], and/or through stimulation of the eicosanoid metabolic pathways [Tesfamariam and Cohen, 1992a,b;Quilley and Chen, 2003]. The major sources of O 2 À in cardiovascular cells are: NADH/NADPH oxidase [Griendling et al, 2000], which transfers electrons from NADH or NADPH to molecular oxygen, producing O 2 À ; xanthine oxidase [Wolin, 1996]; endothelial nitric oxide synthase [Ignarro et al, 1999]; cyclooxygenase-2 [Adeagbo et al, 2003]; myeloperoxidase [Berliner and Heinecke, 1996]; and lipoxygenases [Kunsch and Medford, 1999].…”

Section: Oxidative Stress and Diabetesmentioning

confidence: 99%

Mechanisms of endothelial dysfunction with development of type 1 diabetes mellitus: Role of insulin and C‐peptide

Joshua

Zhang

Falcone

et al. 2005

J of Cellular Biochemistry

View full text Add to dashboard Cite

Complications associated with insulin-dependent diabetes mellitus (type-1diabetes) primarily represent vascular dysfunction that has its origin in the endothelium. While many of the vascular changes are more accountable in the late stages of type-1diabetes, changes that occur in the early or initial functional stages of this disease may precipitate these later complications. The early stages of type-1diabetes are characterized by a diminished production of both insulin and C-peptide with a significant hyperglycemia. During the last decade numerous speculations and theories have been developed to try to explain the mechanisms responsible for the selective changes in vascular reactivity and/or tone and the vascular permeability changes that characterize the development of type-1diabetes. Much of this research has suggested that hyperglycemia and/or the lack of insulin may mediate the observed functional changes in both endothelial cells and vascular smooth muscle. Recent studies suggest several possible mechanisms that might be involved in the observed decreases in vascular nitric oxide (NO) availability with the development of type-1 diabetes. In addition more recent studies have indicated a direct role for both endogenous insulin and C-peptide in the amelioration of the observed endothelial dysfunction. These results suggest a synergistic action between insulin and C-peptide that facilitates increase NO availability and may suggest new clinical treatment modalities for type-1 diabetes mellitus.

show abstract

Role of COX-2 in the Enhanced Vasoconstrictor Effect of Arachidonic Acid in the Diabetic Rat Kidney

Cited by 52 publications

References 28 publications

Effect of Tempol on Renal Cyclooxygenase Expression and Activity in Experimental Diabetes in the Rat

Effect of Tempol on Renal Cyclooxygenase Expression and Activity in Experimental Diabetes in the Rat

Effects of exercise training on the vascular reactivity of the whole kidney circulation in rabbits

Mechanisms of endothelial dysfunction with development of type 1 diabetes mellitus: Role of insulin and C‐peptide

Contact Info

Product

Resources

About