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Effects of losartan and captopril on endothelin-1 production in blood vessels and glomeruli of rats with reduced renal mass.
Am J Hypertens. 1998 Aug; 11(8 Pt 1):989-97.AJ

Abstract

Recently, we have reported that endothelin-1 (ET-1) production is increased in blood vessels and glomeruli of rats with chronic renal failure. This study was design to investigate the role of angiotensin II (Ang II) in endogenous ET-1 production in rats with reduced renal mass. One week after subtotal (5/6) nephrectomy, uremic rats were divided into three groups, and received either no treatment, the Ang II subtype 1 receptor (AT1) antagonist losartan (10 mg/kg/day), or the angiotensin-converting enzyme inhibitor (ACE-I) captopril (30 mg/kg/day) for 6 weeks. Sham-operated rats were used as controls and received no treatment. The levels of immunoreactive ET-1 (ir-ET-1) in plasma and urine, as well as in vascular and renal tissues, were determined by radioimmunoassay (RIA) after extraction. In uremic rats, losartan and captopril completely prevented the increase in systolic blood pressure. At week 6, plasma ir-ET-1 was similar in the different groups of uremic rats and in the controls. However, ir-ET-1 concentration in the mesenteric arterial bed, the thoracic aorta, preglomerular arteries, and glomeruli, as well as urinary ir-ET-1 excretion were significantly greater in uremic-untreated rats compared to controls (P < .01). Treatment of uremic rats with losartan or captopril reduced irET-1 concentration in the thoracic aorta and preglomerular arteries (P < .05), but ir-ET-1 concentration in the mesenteric arterial bed was unchanged. Although both drugs completely prevented the increase in proteinuria, losartan but not captopril significantly reduced ir-ET-1 concentration in glomeruli (P < .05) and normalized urinary ir-ET-1 excretion. This indicates that increased ET-1 production in blood vessels and glomeruli of uremic rats is modulated, at least in part, by Ang II through the AT1 receptor. The beneficial effects of the AT1 antagonist losartan could be attributable to the attenuation of Ang II-induced ET-1 production in this rat remnant kidney model of chronic renal failure, whereas those of the ACE-I captopril are not related to changes in ET-1 production in glomeruli.

Authors+Show Affiliations

Research Centre, CHUQ, L'Hôtel-Dieu de Québec Hospital, Department of Pharmacology, Laval University, Québec, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9715793

Citation

Larivière, R, et al. "Effects of Losartan and Captopril On Endothelin-1 Production in Blood Vessels and Glomeruli of Rats With Reduced Renal Mass." American Journal of Hypertension, vol. 11, no. 8 Pt 1, 1998, pp. 989-97.
Larivière R, Lebel M, Kingma I, et al. Effects of losartan and captopril on endothelin-1 production in blood vessels and glomeruli of rats with reduced renal mass. Am J Hypertens. 1998;11(8 Pt 1):989-97.
Larivière, R., Lebel, M., Kingma, I., Grose, J. H., & Boucher, D. (1998). Effects of losartan and captopril on endothelin-1 production in blood vessels and glomeruli of rats with reduced renal mass. American Journal of Hypertension, 11(8 Pt 1), 989-97.
Larivière R, et al. Effects of Losartan and Captopril On Endothelin-1 Production in Blood Vessels and Glomeruli of Rats With Reduced Renal Mass. Am J Hypertens. 1998;11(8 Pt 1):989-97. PubMed PMID: 9715793.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of losartan and captopril on endothelin-1 production in blood vessels and glomeruli of rats with reduced renal mass. AU - Larivière,R, AU - Lebel,M, AU - Kingma,I, AU - Grose,J H, AU - Boucher,D, PY - 1998/8/26/pubmed PY - 1998/8/26/medline PY - 1998/8/26/entrez SP - 989 EP - 97 JF - American journal of hypertension JO - Am. J. Hypertens. VL - 11 IS - 8 Pt 1 N2 - Recently, we have reported that endothelin-1 (ET-1) production is increased in blood vessels and glomeruli of rats with chronic renal failure. This study was design to investigate the role of angiotensin II (Ang II) in endogenous ET-1 production in rats with reduced renal mass. One week after subtotal (5/6) nephrectomy, uremic rats were divided into three groups, and received either no treatment, the Ang II subtype 1 receptor (AT1) antagonist losartan (10 mg/kg/day), or the angiotensin-converting enzyme inhibitor (ACE-I) captopril (30 mg/kg/day) for 6 weeks. Sham-operated rats were used as controls and received no treatment. The levels of immunoreactive ET-1 (ir-ET-1) in plasma and urine, as well as in vascular and renal tissues, were determined by radioimmunoassay (RIA) after extraction. In uremic rats, losartan and captopril completely prevented the increase in systolic blood pressure. At week 6, plasma ir-ET-1 was similar in the different groups of uremic rats and in the controls. However, ir-ET-1 concentration in the mesenteric arterial bed, the thoracic aorta, preglomerular arteries, and glomeruli, as well as urinary ir-ET-1 excretion were significantly greater in uremic-untreated rats compared to controls (P < .01). Treatment of uremic rats with losartan or captopril reduced irET-1 concentration in the thoracic aorta and preglomerular arteries (P < .05), but ir-ET-1 concentration in the mesenteric arterial bed was unchanged. Although both drugs completely prevented the increase in proteinuria, losartan but not captopril significantly reduced ir-ET-1 concentration in glomeruli (P < .05) and normalized urinary ir-ET-1 excretion. This indicates that increased ET-1 production in blood vessels and glomeruli of uremic rats is modulated, at least in part, by Ang II through the AT1 receptor. The beneficial effects of the AT1 antagonist losartan could be attributable to the attenuation of Ang II-induced ET-1 production in this rat remnant kidney model of chronic renal failure, whereas those of the ACE-I captopril are not related to changes in ET-1 production in glomeruli. SN - 0895-7061 UR - https://www.unboundmedicine.com/medline/citation/9715793/Effects_of_losartan_and_captopril_on_endothelin_1_production_in_blood_vessels_and_glomeruli_of_rats_with_reduced_renal_mass_ L2 - https://academic.oup.com/ajh/article-lookup/doi/10.1016/s0895-7061(98)00088-0 DB - PRIME DP - Unbound Medicine ER -