Role of enhanced glomerular synthesis of thromboxane A2 in progressive kidney disease

Patricia Salvati, Corrado Ferti, Romana G. Ferrario, Ernesto Lamberti, Liliana Duzzi, Giuseppe Bianchi, Giuseppe Remuzzi, Norberto Perico, Ariela Benigni, Paola Braidotti, Guido Coggi, Francesco Pugliese, Carlo Patrono

Research output: Contribution to journalArticle

Abstract

Normotensive rats of the Milan strain (MNS) spontaneously develop focal glomerulosclerosis. In order to explore the contribution of glomerular thromboxane (TX) A2 synthesis to the development of the disease, we have characterized the time course of renal functional and biochemical changes, and their modification by long-term treatment with a TX-synthase inhibitor. Oral administration (150 mg · kg-1 from 1 to 14 months of age) of FCE 22178 suppressed enhanced glomerular TXB2 production at all experimental times (mean inhibition 80%) and proteinuria (varying between 27.1 and 73.0%) while preserving renal blood flow and glomerular filtration rate. These effects of TX-synthase inhibition were seen in the absence of any statistically significant changes in systemic blood pressure. Moreover, FCE 22178 had no antihypertensive effects in hypertensive rats of the Milan strain (MHS) nor in spontaneously hypertensive rats (SHR). Treatment also prevented the age-related hypoalbuminemia and hyperlipidemia observed in control MNS and significantly (P <0.01) reduced glomerular histologic damage, as demonstrated by light microscopy studies and measurement of sclerotic area. We conclude that: 1) MNS rats provide an animal model of long-lasting proteinuria characterized by an age-related increase in glomerular TXB2 production paralleled by progressive loss of renal structural integrity and function and by a secondary dyslipidemia; 2) pharmacological inhibition of glomerular TX-synthase attenuates the structural as well as the functional expression of kidney disease, without a primary effect on systemic blood pressure. These data are suggestive of an important modulating role of TXA2 in the progression of MNS renal disease.

Original languageEnglish
Pages (from-to)447-458
Number of pages12
JournalKidney International
Volume38
Issue number3
Publication statusPublished - Sep 1990

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Thromboxane A2
Thromboxanes
Kidney Diseases
Kidney
Proteinuria
Blood Pressure
Focal Segmental Glomerulosclerosis
Hypoalbuminemia
Renal Circulation
Inbred SHR Rats
Dyslipidemias
Hyperlipidemias
Glomerular Filtration Rate
Antihypertensive Agents
Oral Administration
Microscopy
Animal Models
Pharmacology
Light
Therapeutics

ASJC Scopus subject areas

  • Nephrology

Cite this

Salvati, P., Ferti, C., Ferrario, R. G., Lamberti, E., Duzzi, L., Bianchi, G., ... Patrono, C. (1990). Role of enhanced glomerular synthesis of thromboxane A2 in progressive kidney disease. Kidney International, 38(3), 447-458.

Role of enhanced glomerular synthesis of thromboxane A2 in progressive kidney disease. / Salvati, Patricia; Ferti, Corrado; Ferrario, Romana G.; Lamberti, Ernesto; Duzzi, Liliana; Bianchi, Giuseppe; Remuzzi, Giuseppe; Perico, Norberto; Benigni, Ariela; Braidotti, Paola; Coggi, Guido; Pugliese, Francesco; Patrono, Carlo.

In: Kidney International, Vol. 38, No. 3, 09.1990, p. 447-458.

Research output: Contribution to journalArticle

Salvati, P, Ferti, C, Ferrario, RG, Lamberti, E, Duzzi, L, Bianchi, G, Remuzzi, G, Perico, N, Benigni, A, Braidotti, P, Coggi, G, Pugliese, F & Patrono, C 1990, 'Role of enhanced glomerular synthesis of thromboxane A2 in progressive kidney disease', Kidney International, vol. 38, no. 3, pp. 447-458.
Salvati P, Ferti C, Ferrario RG, Lamberti E, Duzzi L, Bianchi G et al. Role of enhanced glomerular synthesis of thromboxane A2 in progressive kidney disease. Kidney International. 1990 Sep;38(3):447-458.
Salvati, Patricia ; Ferti, Corrado ; Ferrario, Romana G. ; Lamberti, Ernesto ; Duzzi, Liliana ; Bianchi, Giuseppe ; Remuzzi, Giuseppe ; Perico, Norberto ; Benigni, Ariela ; Braidotti, Paola ; Coggi, Guido ; Pugliese, Francesco ; Patrono, Carlo. / Role of enhanced glomerular synthesis of thromboxane A2 in progressive kidney disease. In: Kidney International. 1990 ; Vol. 38, No. 3. pp. 447-458.
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AU - Remuzzi, Giuseppe

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N2 - Normotensive rats of the Milan strain (MNS) spontaneously develop focal glomerulosclerosis. In order to explore the contribution of glomerular thromboxane (TX) A2 synthesis to the development of the disease, we have characterized the time course of renal functional and biochemical changes, and their modification by long-term treatment with a TX-synthase inhibitor. Oral administration (150 mg · kg-1 from 1 to 14 months of age) of FCE 22178 suppressed enhanced glomerular TXB2 production at all experimental times (mean inhibition 80%) and proteinuria (varying between 27.1 and 73.0%) while preserving renal blood flow and glomerular filtration rate. These effects of TX-synthase inhibition were seen in the absence of any statistically significant changes in systemic blood pressure. Moreover, FCE 22178 had no antihypertensive effects in hypertensive rats of the Milan strain (MHS) nor in spontaneously hypertensive rats (SHR). Treatment also prevented the age-related hypoalbuminemia and hyperlipidemia observed in control MNS and significantly (P <0.01) reduced glomerular histologic damage, as demonstrated by light microscopy studies and measurement of sclerotic area. We conclude that: 1) MNS rats provide an animal model of long-lasting proteinuria characterized by an age-related increase in glomerular TXB2 production paralleled by progressive loss of renal structural integrity and function and by a secondary dyslipidemia; 2) pharmacological inhibition of glomerular TX-synthase attenuates the structural as well as the functional expression of kidney disease, without a primary effect on systemic blood pressure. These data are suggestive of an important modulating role of TXA2 in the progression of MNS renal disease.

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