Modulating role for thromboxane in the tubuloglomerular feedback response in the rat.

Welch, William J.; Wilcox, Christopher S.

doi:10.1172/jci113529

Cited by 47 publications

(35 citation statements)

References 16 publications

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“…TXA2 is one of the factors modulating the tubuloglomerular feedback response (24) and may be important to maintain glomeru lar filtration rate in some cases. In fact, it has been report ed (25) that TXA2 could contribute to the increase of glomerular filtration rate in the hypoperfused kidney.…”

Section: Resultsmentioning

confidence: 99%

Effects of KW-3635, a Specific Thromboxane A2-Receptor Antagonist, on the Development of Lupus Nephritis in NZB × NZW F1 Mice

Kawakage

Mizumoto

Nukui

et al. 1993

Japanese Journal of Pharmacology

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ABSTRACT-We examined the effect of KW-3635, a specific thromboxane A2 (TXA2)-receptor antagonist, on the development of lupus nephritis in NZB x NZW Fl mice. KW-3635 was orally given once a day for 33 weeks beginning at eight weeks of age. In the control group, the mice began to die at 39 weeks of age, show ing severe proteinuria and histopathologic abnormality in the renal glomeruli. Administration of KW-3635 (30 mg/kg/day) significantly reduced urinary protein excretion (1.7±0.9 vs. 8.5±2.4 mg/6 hr/mouse, P<0.01), mortality (1/18 vs. 6/19, P<0.05) and the histopathologic score of the kidney examined at 41 weeks of age. Thus, chronic administration of KW-3635 markedly attenuated the renal disease in NZB x NZW F1 mice, suggesting that TXA2 is an important mediator of the pathogenesis in this murine model of lupus nephritis.

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Section: Resultsmentioning

confidence: 99%

Effects of KW-3635, a Specific Thromboxane A2-Receptor Antagonist, on the Development of Lupus Nephritis in NZB × NZW F1 Mice

Kawakage

Mizumoto

Nukui

et al. 1993

Japanese Journal of Pharmacology

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“…Thromboxane is a potent vasoconstrictor 47 and could contribute to salt retention and vasoconstriction by potentiation of the tubuloglomerular feedback mechanism. 13 Moreover, the inhibition of thromboxane synthesis attenuates vascular responses to sympathetic nerve stimulation. 48 Increased TxB 2 synthesis stimulated by Ang II may have increased the release of, or responsiveness to, sympathetic neurotransmitters and thereby facilitated the development of hypertension.…”

Section: Discussionmentioning

confidence: 99%

“…The details of the purification and assay methods used, the performance characteristics of the assay, and the validation procedures have been published. 13 The sensitivity of the PG method used was 2-5 pg/sample for TxB 2 and 5-10 pg/sample for 6kPGF la and PGE 2 . The interassay coefficient of variation (n=31) for TxB 2 was 7.6%, for 6kPGF la was 8.3%, and for PGE 2 was 9.2%.…”

Section: Measurement Of Nerve Activitymentioning

confidence: 99%

Angiotensin-induced hypertension in the rat. Sympathetic nerve activity and prostaglandins.

et al. 1989

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To elucidate mechanisms of angiotensin II (Ang II)-related hypertension, we infused angiotensin (76 ng/min s.c.) into rats with minipumps for 10-14 days. Control rats received sham pumps. We measured blood pressure by tail-cuff, and the excretion of aldosterone and prostaglandins (PG) (PGE 2 , prostacyclin derivative 6kPGF, a , and thromboxane [Tx] derivative TxB 2 ). Angiotensin II increased blood pressure by 20 mm Hg by day 2 and by 90 mm Hg by day 10. Aldosterone excretion increased from 10 to 70 ng/day in Ang II rats by day 7. Urine PGE 2 did not increase in angiotensin rats; however, both 6kPGF, a and TxB 2 excretion increased with angiotensin. Control rats had no changes in any of these parameters. A sympathetic component was tested in a separate group of angiotensin rats that received phenoxybenzamine (300 Mg/kg/day) during angiotensin infusion; their increase in blood pressure of 40 mm Hg at 10 days was less than in those rats with angiotensin alone but more than in control rats. Phenoxybenzamine did not influence the angiotensin-induced increases in excretion of 6kPGF la or TxB 2 . Additional groups of conscious angiotensin and control rats were equipped with splanchnic nerve electrodes on day 14 for recording of sympathetic nerve activity. Angiotensin rats had greater basal sympathetic nerve activity than the control rats. Incremental methoxamine injections demonstrated altered baroreceptor reflex function in rats receiving angiotensin. We conclude that increased blood pressure with chronic angiotensin infusion is accompanied by increased production of aldosterone and increased sympathetic tone. The latter may be modulated by PG. {Hypertension 1989;14:396-403) A ngiotensin II (Ang II) is intimately involved in / \ the homeostatic regulation of blood pres-.Z \ . sure and body fluids, although the details of its mechanisms of action remain quite controversial. 1In addition to a well-characterized vasoconstrictor action, Ang II has also been proposed to increase peripheral vascular resistance indirectly through peripheral and central mechanisms that lead to an increased activity of the sympathetic nervous system.2 -4 Further, Ang II causes sodium retention both by a direct action on the renal tubule, 5 and through the stimulation of aldosterone release. 5Finally, Ang II administration influences the plasma concentration, renal excretion, and tissue generation of prostaglandins (PGs) that modulate the vasoconstriction.6 However, the relevance of some of these studies to the pathophysiological role of Ang II in hypertension is not clear, as many were conducted during short-term Ang II infusion in animals under anesthesia.To further define mechanisms in the production of Ang II-related hypertension, we infused Ang II into conscious rats over a 14-day period. We measured sympathetic nervous system activity directly with bipolar electrodes implanted on their splanchnic nerves. We determined the excretion of aldosterone and PG (PGE2, 6kPGFi a , and thromboxane [Tx]B 2 ). To further investigate the role of the s...

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“…PGE 2 . The details used for the assay, including dual system purification by organic excretion and thin layer chromatography, individual sample recovery, limits of detection, intra-and interassay coefficients of variation, cross-reactivity, and validation against GCMS, have been published (20).…”

Section: -Iso Pgfmentioning

confidence: 99%

Salt Intake, Oxidative Stress, and Renal Expression of NADPH Oxidase and Superoxide Dismutase

Kitiyakara

Chabrashvili²,

Chen³

et al. 2003

Journal of the American Society of Nephrology

281

236

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Abstract. The hypothesis that a high salt (HS) intake increases oxidative stress was investigated and was related to renal cortical expression of NAD(P)H oxidase and superoxide dismutase (SOD). 8-Isoprostane PGF 2␣ and malonyldialdehyde were measured in groups (n ϭ 6 to 8) of conscious rats during low-salt, normal-salt, or HS diets. NADPH-and NADH-stimulated superoxide anion (O 2 ·Ϫ ) generation was assessed by chemiluminescence, and expression of NAD(P)H oxidase and SOD were assessed with real-time PCR. Excretion of 8-isoprostane and malonyldialdehyde increased incrementally twoto threefold with salt intake (P Ͻ 0.001), whereas prostaglandin E 2 was unchanged. Renal cortical NADH-and NADPHstimulable O 2 ·Ϫ generation increased (P Ͻ 0.05) 30 to 40% with salt intake. Compared with low-salt diet, HS significantly (P Ͻ 0.005) increased renal cortical mRNA expression of gp91 phox and p47 phox and decreased expression of intracellular CuZn (IC)-SOD and mitochondrial (Mn)-SOD. Despite suppression of the renin-angiotensin system, salt loading enhances oxidative stress. This is accompanied by increased renal cortical NADH and NADPH oxidase activity and increased expression of gp91 phox and p47 phox and decreased IC-and Mn-SOD. Thus, salt intake enhances generation of O 2 ·Ϫ accompanied by enhanced renal expression and activity of NAD(P)H oxidase with diminished renal expression of IC-and Mn-SOD.

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Modulating role for thromboxane in the tubuloglomerular feedback response in the rat.

Cited by 47 publications

References 16 publications

Effects of KW-3635, a Specific Thromboxane A2-Receptor Antagonist, on the Development of Lupus Nephritis in NZB × NZW F1 Mice

Effects of KW-3635, a Specific Thromboxane A2-Receptor Antagonist, on the Development of Lupus Nephritis in NZB × NZW F1 Mice

Angiotensin-induced hypertension in the rat. Sympathetic nerve activity and prostaglandins.

Salt Intake, Oxidative Stress, and Renal Expression of NADPH Oxidase and Superoxide Dismutase

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