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Renal and vascular effects of chronic endothelin receptor antagonism in malignant hypertensive rats.
Am J Hypertens. 1996 Aug; 9(8):803-11.AJ

Abstract

The effect of the combined ETA/ETB endothelin receptor antagonist bosentan on blood pressure, vascular hypertrophy, and pathologic renal changes was investigated in a model of malignant hypertension, severe vascular hypertrophy, and enhanced vascular expression of endothelin-1, the deoxycorticosterone acetate (DOCA), and salt-treated spontaneously hypertensive rat (SHR). DOCA-salt treated SHR received 100 mg bosentan per kilogram weight per day mixed with their food. Systolic blood pressure of untreated DOCA-salt SHR rose to 241 +/- 1.5 mm Hg, whereas that of bosentan-treated rats rose to 221 +/- 5.1 mm Hg (P < .01). Cardiac and conduit artery mass were not affected by treatment. Small arteries from the coronary, renal, and mesenteric circulations showed a smaller media width and cross-sectional area of the media in rats treated with bosentan than in untreated rats. The kidneys showed the presence of fibrinoid necrosis in a high percentage of afferent arterioles and glomeruli of untreated DOCA-SHR. Some kidneys of treated rats exhibited less severe vascular hypertrophy and lesser extent of vascular or glomerular fibrinoid necrosis, but the renal injury score of bosentan-treated DOCA-SHR was only at the limit of significance from that of untreated rats (P = .06). These results suggest a role for endothelin-1 in blood pressure elevation and the severe vascular hypertrophy of small arteries of the coronary, renal, and mesenteric vasculature, but not of the heart or larger conduit vessels in the malignant hypertension that SHR develop after treatment with DOCA and salt. Although some bosentan-treated rats showed fewer renal lesions, a significant effect on renal pathology could not be unambiguously demonstrated. Further studies will be necessary to determine whether endothelin antagonists may indeed offer some degree of renal protection and have therapeutic potential in severe or malignant hypertension.

Authors+Show Affiliations

Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montrèal, Québec, Canada.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

8862227

Citation

Li, J S., et al. "Renal and Vascular Effects of Chronic Endothelin Receptor Antagonism in Malignant Hypertensive Rats." American Journal of Hypertension, vol. 9, no. 8, 1996, pp. 803-11.
Li JS, Schürch W, Schiffrin EL. Renal and vascular effects of chronic endothelin receptor antagonism in malignant hypertensive rats. Am J Hypertens. 1996;9(8):803-11.
Li, J. S., Schürch, W., & Schiffrin, E. L. (1996). Renal and vascular effects of chronic endothelin receptor antagonism in malignant hypertensive rats. American Journal of Hypertension, 9(8), 803-11.
Li JS, Schürch W, Schiffrin EL. Renal and Vascular Effects of Chronic Endothelin Receptor Antagonism in Malignant Hypertensive Rats. Am J Hypertens. 1996;9(8):803-11. PubMed PMID: 8862227.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Renal and vascular effects of chronic endothelin receptor antagonism in malignant hypertensive rats. AU - Li,J S, AU - Schürch,W, AU - Schiffrin,E L, PY - 1996/8/1/pubmed PY - 1996/8/1/medline PY - 1996/8/1/entrez SP - 803 EP - 11 JF - American journal of hypertension JO - Am J Hypertens VL - 9 IS - 8 N2 - The effect of the combined ETA/ETB endothelin receptor antagonist bosentan on blood pressure, vascular hypertrophy, and pathologic renal changes was investigated in a model of malignant hypertension, severe vascular hypertrophy, and enhanced vascular expression of endothelin-1, the deoxycorticosterone acetate (DOCA), and salt-treated spontaneously hypertensive rat (SHR). DOCA-salt treated SHR received 100 mg bosentan per kilogram weight per day mixed with their food. Systolic blood pressure of untreated DOCA-salt SHR rose to 241 +/- 1.5 mm Hg, whereas that of bosentan-treated rats rose to 221 +/- 5.1 mm Hg (P < .01). Cardiac and conduit artery mass were not affected by treatment. Small arteries from the coronary, renal, and mesenteric circulations showed a smaller media width and cross-sectional area of the media in rats treated with bosentan than in untreated rats. The kidneys showed the presence of fibrinoid necrosis in a high percentage of afferent arterioles and glomeruli of untreated DOCA-SHR. Some kidneys of treated rats exhibited less severe vascular hypertrophy and lesser extent of vascular or glomerular fibrinoid necrosis, but the renal injury score of bosentan-treated DOCA-SHR was only at the limit of significance from that of untreated rats (P = .06). These results suggest a role for endothelin-1 in blood pressure elevation and the severe vascular hypertrophy of small arteries of the coronary, renal, and mesenteric vasculature, but not of the heart or larger conduit vessels in the malignant hypertension that SHR develop after treatment with DOCA and salt. Although some bosentan-treated rats showed fewer renal lesions, a significant effect on renal pathology could not be unambiguously demonstrated. Further studies will be necessary to determine whether endothelin antagonists may indeed offer some degree of renal protection and have therapeutic potential in severe or malignant hypertension. SN - 0895-7061 UR - https://www.unboundmedicine.com/medline/citation/8862227/Renal_and_vascular_effects_of_chronic_endothelin_receptor_antagonism_in_malignant_hypertensive_rats_ L2 - https://academic.oup.com/ajh/article-lookup/doi/10.1016/0895-7061(96)00100-8 DB - PRIME DP - Unbound Medicine ER -