Renal effects of the inhibitor of thromboxane A2-synthetase OKY-046

Hatziantoniou, C.; Papanikolaou, Nikolaos

doi:10.1007/bf01955558

Cited by 15 publications

(8 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At this point, the argument is hypothetical, but it is not unreasonable to propose that the increased NOS activity is a response to significant vasoconstrictor stimulation in the established ARF kidney. Endogenous vasoconstrictor agonist activity, including endothelin-1, thromboxane A2, and renin-angiotensin, has been shown to be increased in ischemic ARF models (29)(30)(31). These agonists, in addition to endothelin-3, have been shown to induce endothelial NOS activity (32)(33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

Increased nitric oxide synthase activity despite lack of response to endothelium-dependent vasodilators in postischemic acute renal failure in rats.

Conger

Robinette²,

Villar³

et al. 1995

J. Clin. Invest.

113

View full text Add to dashboard Cite

Lack of response to endothelium-dependent vasodilators generally has been considered to be evidence for decreased nitric oxide synthase (NOS) activity and NO generation after ischemic or hypoxic injury to vital organs including the kidney. In this study, renal blood flow (RBF) responses to endothelium-dependent vasodilators acetylcholine and bradykinin and the endothelium-independent vasodilator prostacyclin, the nonselective NOS inhibitor L-NAME (without and with L-arginine), the inducible NOS inhibitor aminoguanidine, and the NO-donor sodium nitroprusside were examined in 1-wk norepinephrine-induced (NE) and sham-induced acute renal failure (ARF) rats. Compared with sham-ARF, there was no increase in RBF to intrarenal acetylcholine and bradykinin, but a comparable RBF increase to prostacyclin in NE-ARF kidneys. However, there was a signiflcantiy greater decline in RBF to intravenous L-NAME in NE-than sham-ARF rats (-65±8 vs. -37±5%, P < 0.001) which was completely blocked by prior L-arginine infusion. There was no change in RBF to the inducible NOS specific inhibitor aminoguanidine. Unlike sham-ARF, there was no increase in RBF to intrarenal sodium nitroprusside in NE-ARF. Immunohistochemistry and immunofluorescence detection of constitutive (c) NOS using mouse monoclonal antibody were carried out to positively determine the presence of cNOS in NE-ARF. 90% of renal resistance vessels showed evidence of endothelial cNOS in both sham-and NE-ARF. Taken together, results of these experiments are consistent with the conclusion that NOS/NO activity is, in fact, maximal at baseline in 1-wk NE-ARF and cannot be increased further by exogenous stimuli of NOS activity. The increased NOS is likely of the constitutive form and of endothelial origin. It is suggested that the increased NOS activity Clin. Invest. 1995. 96:631-638.)

show abstract

Section: Discussionmentioning

confidence: 99%

Increased nitric oxide synthase activity despite lack of response to endothelium-dependent vasodilators in postischemic acute renal failure in rats.

Conger

Robinette²,

Villar³

et al. 1995

J. Clin. Invest.

113

View full text Add to dashboard Cite

show abstract

“…The following parameters were measured: (1) Urinary and serum creatinine concentrations were deter mined by a method utilizing Fuller's earth in order to eliminate chro mogens [10,11]. Creatinine clearance (Ccr) was calculated as usual.…”

Section: Methodsmentioning

confidence: 99%

“…In previous studies it has been found that infusion of PGs [13][14][15][16] or inhibition ofTXA2 synthesis [10][11][12] pro tected against the development of ARF. Because CsA enhanced TXB2 (TXA2) and diminished PGs, we ex pected the NT induced by this agent to be more serious than that induced by substances such as glycerol (GRL) [10,11], mercuric chloride (MC) [24] and gentamicin (GM) [12] which were found to enhance both TXA2 and PG production.…”

Section: Effect O F Csa In Normal Ratsmentioning

confidence: 99%

“…Because CsA enhanced TXB2 (TXA2) and diminished PGs, we ex pected the NT induced by this agent to be more serious than that induced by substances such as glycerol (GRL) [10,11], mercuric chloride (MC) [24] and gentamicin (GM) [12] which were found to enhance both TXA2 and PG production.…”

Section: Effect O F Csa In Normal Ratsmentioning

confidence: 99%

“…This agent also antagonizes the amplifying effects of 5-HT on other vasoconstrictor substances, such as catecholamines (ai adrenergic receptors), histamine (H2 histaminergic receptors) and PGF2o [9], Since it has been observed in previous studies that the metabolites of arachidonic acid play an important role in development, thromboxane (TXA2) [10][11][12], or in protec tion, prostaglandins (PGE!, PGE2, PGI2) [13][14][15][16], against acute renal failure (ARF), in our studies we also examined the role of these agents.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effect of Ketanserine in Cyclosporine-lnduced Renal Dysfunction in Rats

Darlametsos¹,

Morphake²,

Bariéty

et al. 1995

Nephron

Self Cite

View full text Add to dashboard Cite

Cyclosporine (CsA)-treated female Wistar rats, in dose of 37.5 μM (45 mg)/ kg/day for 7 days, exhibited significantly decreased creatinine clearance (Ccr), and provoked body weight loss (BWL), which is consistent with the development of nephrotoxicity (NT). Urine volume (V) did not change and proteinuria (PU) was not provoked. These changes were associated with significantly diminished ratios of urinary PGE₂/TXB₂ and 6kPGF_1α/TXB₂ excretions. Light-microscopic (LM) sections of rat kidneys showed that all kidneys were affected but the lesions (mainly diffuse vacuolization) were reversible. When CsA-treated animals were pretreated with ketanserine (KTS), which antagonizes (a) the direct vasoconstrictor effect of serotonin (5-HT), and (b) the amplifying effects of 5-HT on other vasoactive substances (such as noradrenaline (NA), α₁-receptors, histamine, H₂ receptors, and prostaglandin F_2α), Ccr and urine volume significantly increased, BWL was partially prevented and the ratios of urinary PGE₂/TXB₂ and 6kPGF_1α/TXB₂ excretions were significantly enhanced. LM sections showed that only 5 of 9 rats were affected but the lesions were of less importance. These observations indicate that the NT induced by CsA in our studies was mediated by 5-HT, a potent vasoconstrictor agent, and by the metabolites of arachidonic acid. However, other vasoactive agents and additional mechanisms could also be implicated.

show abstract

Alteration of mercuric chloride-induced autoimmune glomerulonephritis in Brown-Norway rats by herring oil, evening primrose oil and OKY-046 a selective TXA-synthetase inhibitor

Papanikolaou

1987

Prostaglandins, Leukotrienes and Medicine

View full text Add to dashboard Cite

Renal effects of the inhibitor of thromboxane A2-synthetase OKY-046

Cited by 15 publications

References 27 publications

Increased nitric oxide synthase activity despite lack of response to endothelium-dependent vasodilators in postischemic acute renal failure in rats.

Increased nitric oxide synthase activity despite lack of response to endothelium-dependent vasodilators in postischemic acute renal failure in rats.

Effect of Ketanserine in Cyclosporine-lnduced Renal Dysfunction in Rats

Alteration of mercuric chloride-induced autoimmune glomerulonephritis in Brown-Norway rats by herring oil, evening primrose oil and OKY-046 a selective TXA-synthetase inhibitor

Contact Info

Product

Resources

About