Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q92565 (GFR)
 4,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Short-term cholesterol feeding has been shown to cause impaired vasodilatation in response to acetylcholine. The present study of renal hemodynamics was carried out to examine the role of thromboxane/PGH2 in mediating this abnormal response. In normal rats (ND), infusion of acetylcholine into the suprarenal aorta caused marked increases in renal blood flow, GFR, single nephron glomerular filtration rate, single nephron afferent plasma flow, and ultrafiltration coefficient, accompanied by a fall in preglomerular resistance. In cholesterol fed rats (CSD), the response to acetylcholine was markedly blunted. Infusion of L-arginine, the precursor to nitric oxide (NO), caused comparable renal vasodilatation in ND and CSD rats, implying that the ability to synthesize NO from its precursor was not severely impaired in the CSD animals. The observations do not exclude, however, the possibility of impaired synthesis of NO from endogenous precursor. In additional experiments, we infused a TxA2/PGH2 receptor antagonist in CSD rats and then administered acetylcholine. Renal vasodilatation occurred to a degree indistinguishable from that in ND rats given acetylcholine alone. When ND rats were infused with the same combination of the TxA2/PGH2 receptor antagonist and acetylcholine, renal vasodilatation was also significantly greater than with acetylcholine alone. This suggests that acetylcholine initiates release of vasoconstrictor prostanoids as well as NO from vascular endothelium. This was observed in ND as well as in CSD animals. Because LDL increases the supply of arachidonic acid for prostaglandin synthesis, we postulate that greater amounts of PGH2/TxA2 are synthesized via calcium activation of phospholipase A2 when acetylcholine is administered to CSD animals. This may account in large measure for the blunted vasodilatation to acetylcholine.
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PMID:Role of thromboxane in impaired renal vasodilatation response to acetylcholine in hypercholesterolemic rats. 156 3

Depression of GFR and antinatriuresis in response to high chloride has been linked to a cyclooxygenase (COX)-dependent mechanism involving thromboxane A2 (TxA2) and prostaglandin endoperoxide (PGH2), because inhibition of COX prevented the fall in GFR and antinatriuresis produced by hyperchloremia. However, hyperchloremia did not increase, but unexpectedly decreased, renal prostaglandin and TxA2 efflux (Yin et al., 1995). To resolve questions regarding the role of eicosanoids in mediating the renal functional effects of high chloride (117 mM), by stimulating either TxA2 synthesis or TxA2/PGH2 receptors, we compared the ability of indomethacin to block high-chloride effects in the rat isolated kidney with that of BMS 180291 and SQ 29548, antagonists of the TxA2/PGH2 receptor. These antagonists differ in terms of their selectivity and their capacity to inhibit isoforms of the TxA2/PGH2 receptor. Indomethacin and SQ 29548 had identical actions, preventing the decrease of GFR and antinatriuresis evoked by hyperchloremia, e.g., sodium excretion rate in the SQ 29548 and indomethacin groups increased to 7.2 +/- 1.3 and 7.1 +/- 1.2 microEq/min, respectively, compared with 2.6 +/- 0.7 microEq/min in the control group. In contrast, neither BMS 180291 nor the TxA2 synthase inhibitors, OKY 046 and CGS 13080, modified the negative effects of high chloride on GFR or sodium excretion. These results argue against either TxA2 or PGH2 acting as mediator of the effects of high chloride on renal function and suggest a product of COX activity such as a 20-HETE analog of prostaglandin endoperoxide. Evidence to support this proposal was obtained: 1) Hyperchloremia increased 20-HETE release from the rat kidney by 2-fold when compared with low-chloride conditions of renal perfusion. 2) The renal vasoconstrictor action of 20-HETE was shown to be dependent on COX activity and to be antagonized by blockade of the TxA2/PGH2 receptor.
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PMID:Analysis of eicosanoid mediation of the renal functional effects of hyperchloremia. 922 45

Patients with intra- or extrahepatic bile-duct obstruction are susceptible to acute renal failure (ARF) especially when undergoing major surgery. We observed in jaundiced rats 4 days after bile-duct ligation (BDL) a decrease in GFR accompanied by polyuria which is associated with increased urinary thromboxane (TX) excretion and glomerular TXB2 synthesis. The TXA2/ PGH2 receptor antagonist daltroban normalized GFR but not urine concentration. There was also a rise in plasma and urinary endothelin (ET-1) with increased papillary ET synthesis. The ETA/ETB receptor blocker bosentan restored GFR and the renal concentrating ability. Since we showed previously that ET-induced decreases in renal perfusion and ultrafiltration coefficient Kf are mediated by other autacoids such as TX, this may explain why both bosentan and daltroban normalized GFR. These results suggest that increased renal glomerular TX and vascular and inner medullary collecting duct ET synthesis contribute to defective GFR and distal tubular function in experimental BDL. Similar alterations may also predispose the human kidney to ARF in patients with obstructive jaundice.
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PMID:Impaired renal function in obstructive jaundice: roles of the thromboxane and endothelin systems. 938 Feb 22