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Angiotensin II receptor blockade limits kidney injury in two-kidney, one-clip Goldblatt hypertensive rats with special reference to phenotypic changes.
J Lab Clin Med. 1999 Feb; 133(2):134-43.JL

Abstract

Recent evidence indicates that tubulointerstitial injury plays an important role in hypertensive kidney injury and that phenotypic changes contribute to this pathology. Moreover, angiotensin II is known to be actively involved in the pathogenesis of progressive kidney injury induced by hypertension. The present study was undertaken to see the effect of a newly developed angiotensin II type I receptor (AT1 receptor) antagonist on hypertension-induced kidney injury and to determine the contribution of phenotypic changes to morphologic alterations. Two-kidney, one-clip (2K1C), Goldblatt hypertensive rats (n = 27) were made by clipping the left renal artery. These animals were orally administered 57G709 (a selective non-peptide AT1 receptor antagonist)(10 mg/kg/day), captopril (20 mg/kg/day), or vehicle alone for 23 days beginning 4 weeks after clipping. In the non-clipped kidney of vehicle-treated 2K1 C rats, marked tubulointerstitial injury as well as glomerular sclerosis and/or hyalinosis was found in association with phenotypic changes, as shown by the neoexpression of vimentin in periglomeruli, perivascular walls, distal tubuli, and injured interstitium. Renin expression was markedly suppressed in the non-clipped kidneys of vehicle-treated 2K1C rats as compared with renin expression in normotensive control kidneys of sham-operated rats. Both 57G709 and captopril markedly ameliorated hypertensive kidney injury as reflected by the glomerular sclerosing index and by the tubulointerstitial index as determined by the point-counting method, and this improvement was accompanied by a significant decrease in blood pressure, urinary protein excretion, kidney/body weight ratio, and heart/body weight ratio. In addition, the vimentin neoexpression mentioned above was also suppressed with an inhibition of angiotensin II. These results suggest that in 2K1C Goldblatt hypertensive kidney injury, the AT1 receptor antagonist 57G709 exerts a potent renal protective effect associated with the inhibition of phenotypic changes.

Authors+Show Affiliations

Second Department of Internal Medicine, National Defense Medical College, Tokorozawa, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9989765

Citation

Kobayashi, S, et al. "Angiotensin II Receptor Blockade Limits Kidney Injury in Two-kidney, One-clip Goldblatt Hypertensive Rats With Special Reference to Phenotypic Changes." The Journal of Laboratory and Clinical Medicine, vol. 133, no. 2, 1999, pp. 134-43.
Kobayashi S, Ishida A, Moriya H, et al. Angiotensin II receptor blockade limits kidney injury in two-kidney, one-clip Goldblatt hypertensive rats with special reference to phenotypic changes. J Lab Clin Med. 1999;133(2):134-43.
Kobayashi, S., Ishida, A., Moriya, H., Mori, N., Fukuda, T., & Takamura, T. (1999). Angiotensin II receptor blockade limits kidney injury in two-kidney, one-clip Goldblatt hypertensive rats with special reference to phenotypic changes. The Journal of Laboratory and Clinical Medicine, 133(2), 134-43.
Kobayashi S, et al. Angiotensin II Receptor Blockade Limits Kidney Injury in Two-kidney, One-clip Goldblatt Hypertensive Rats With Special Reference to Phenotypic Changes. J Lab Clin Med. 1999;133(2):134-43. PubMed PMID: 9989765.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Angiotensin II receptor blockade limits kidney injury in two-kidney, one-clip Goldblatt hypertensive rats with special reference to phenotypic changes. AU - Kobayashi,S, AU - Ishida,A, AU - Moriya,H, AU - Mori,N, AU - Fukuda,T, AU - Takamura,T, PY - 1999/2/16/pubmed PY - 1999/2/16/medline PY - 1999/2/16/entrez SP - 134 EP - 43 JF - The Journal of laboratory and clinical medicine JO - J. Lab. Clin. Med. VL - 133 IS - 2 N2 - Recent evidence indicates that tubulointerstitial injury plays an important role in hypertensive kidney injury and that phenotypic changes contribute to this pathology. Moreover, angiotensin II is known to be actively involved in the pathogenesis of progressive kidney injury induced by hypertension. The present study was undertaken to see the effect of a newly developed angiotensin II type I receptor (AT1 receptor) antagonist on hypertension-induced kidney injury and to determine the contribution of phenotypic changes to morphologic alterations. Two-kidney, one-clip (2K1C), Goldblatt hypertensive rats (n = 27) were made by clipping the left renal artery. These animals were orally administered 57G709 (a selective non-peptide AT1 receptor antagonist)(10 mg/kg/day), captopril (20 mg/kg/day), or vehicle alone for 23 days beginning 4 weeks after clipping. In the non-clipped kidney of vehicle-treated 2K1 C rats, marked tubulointerstitial injury as well as glomerular sclerosis and/or hyalinosis was found in association with phenotypic changes, as shown by the neoexpression of vimentin in periglomeruli, perivascular walls, distal tubuli, and injured interstitium. Renin expression was markedly suppressed in the non-clipped kidneys of vehicle-treated 2K1C rats as compared with renin expression in normotensive control kidneys of sham-operated rats. Both 57G709 and captopril markedly ameliorated hypertensive kidney injury as reflected by the glomerular sclerosing index and by the tubulointerstitial index as determined by the point-counting method, and this improvement was accompanied by a significant decrease in blood pressure, urinary protein excretion, kidney/body weight ratio, and heart/body weight ratio. In addition, the vimentin neoexpression mentioned above was also suppressed with an inhibition of angiotensin II. These results suggest that in 2K1C Goldblatt hypertensive kidney injury, the AT1 receptor antagonist 57G709 exerts a potent renal protective effect associated with the inhibition of phenotypic changes. SN - 0022-2143 UR - https://www.unboundmedicine.com/medline/citation/9989765/Angiotensin_II_receptor_blockade_limits_kidney_injury_in_two_kidney_one_clip_Goldblatt_hypertensive_rats_with_special_reference_to_phenotypic_changes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-2143(99)90006-9 DB - PRIME DP - Unbound Medicine ER -