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Endothelin and gelatinases in renal changes following blockade of nitric oxide synthase in hypertensive rats.
Chin J Physiol. 2008 Jun 30; 51(3):186-95.CJ

Abstract

We investigated the involvement of matrix metalloproteinases (MMPs), tissue inhibitor (TIMP) and endothelin-1 (ET-1) in the renal damage in spontaneously hypertensive rats (SHR) following nitric oxide (NO) deprivation. SHR received Nomega-nitro-L-arginine methyl ester (L-NAME) from 5 wk-old for a period of 30 days. An ETA antagonist, FR139317 was used. We gave SHR FR139317 alone and cotreatment with L-NAME. L-NAME caused systemic hypertension, decrease in plasma nitrate/nitrite, increases in blood urea nitrogen and creatinine, impairment of glomerular dynamics. NO deprivation reduced the renal tissue cGMP, but it increased the collagen volume fraction, number of sclerotic glomeruli, arteriolar injury score and glomerular injury score. In addition, L-NAME elevated the plasma ET-1 at day 5. Cotreatment with FR139317 alleviated the L-NAME-induced functional and structural changes of renal glomeruli. L-NAME administration for 5 to 10 days resulted in decreases in MMP2 and MMP9 with increasing TIMP2. After L-NAME for 15 days, opposite changes (increases in MMP2 and MMP9 with a decrease in TIMP2) were observed. FR139317 cotreatment ameliorated the L-NAME-induced changes in MMP2 and MMP9 throughout the 30-day observation period. The ETA antagonist cotreatment attenuated the L-NAME-induced increase in TIMP2 before day 15, but not after day 20. The results indicate that ET-1, MMPs and TIMP are involved at the early stage (before 10 days) of glomerular sclerosis and arteriosclerosis with functional impairment following NO deprivation. The changes in MMPs and TIMP at the late stage (after 20 days) may be a compensatory response to prevent further renal damage.

Authors+Show Affiliations

Institute of Biotechnology, National Chia-Yi University, Chiayi Republic of China.No 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

18935914

Citation

Yang, Yi-Ling, et al. "Endothelin and Gelatinases in Renal Changes Following Blockade of Nitric Oxide Synthase in Hypertensive Rats." The Chinese Journal of Physiology, vol. 51, no. 3, 2008, pp. 186-95.
Yang YL, Liu DD, Hsieh NK, et al. Endothelin and gelatinases in renal changes following blockade of nitric oxide synthase in hypertensive rats. Chin J Physiol. 2008;51(3):186-95.
Yang, Y. L., Liu, D. D., Hsieh, N. K., & Chen, H. I. (2008). Endothelin and gelatinases in renal changes following blockade of nitric oxide synthase in hypertensive rats. The Chinese Journal of Physiology, 51(3), 186-95.
Yang YL, et al. Endothelin and Gelatinases in Renal Changes Following Blockade of Nitric Oxide Synthase in Hypertensive Rats. Chin J Physiol. 2008 Jun 30;51(3):186-95. PubMed PMID: 18935914.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endothelin and gelatinases in renal changes following blockade of nitric oxide synthase in hypertensive rats. AU - Yang,Yi-Ling, AU - Liu,Demeral David, AU - Hsieh,Nan-Kuang, AU - Chen,Hsing I, PY - 2008/10/22/pubmed PY - 2008/12/17/medline PY - 2008/10/22/entrez SP - 186 EP - 95 JF - The Chinese journal of physiology JO - Chin J Physiol VL - 51 IS - 3 N2 - We investigated the involvement of matrix metalloproteinases (MMPs), tissue inhibitor (TIMP) and endothelin-1 (ET-1) in the renal damage in spontaneously hypertensive rats (SHR) following nitric oxide (NO) deprivation. SHR received Nomega-nitro-L-arginine methyl ester (L-NAME) from 5 wk-old for a period of 30 days. An ETA antagonist, FR139317 was used. We gave SHR FR139317 alone and cotreatment with L-NAME. L-NAME caused systemic hypertension, decrease in plasma nitrate/nitrite, increases in blood urea nitrogen and creatinine, impairment of glomerular dynamics. NO deprivation reduced the renal tissue cGMP, but it increased the collagen volume fraction, number of sclerotic glomeruli, arteriolar injury score and glomerular injury score. In addition, L-NAME elevated the plasma ET-1 at day 5. Cotreatment with FR139317 alleviated the L-NAME-induced functional and structural changes of renal glomeruli. L-NAME administration for 5 to 10 days resulted in decreases in MMP2 and MMP9 with increasing TIMP2. After L-NAME for 15 days, opposite changes (increases in MMP2 and MMP9 with a decrease in TIMP2) were observed. FR139317 cotreatment ameliorated the L-NAME-induced changes in MMP2 and MMP9 throughout the 30-day observation period. The ETA antagonist cotreatment attenuated the L-NAME-induced increase in TIMP2 before day 15, but not after day 20. The results indicate that ET-1, MMPs and TIMP are involved at the early stage (before 10 days) of glomerular sclerosis and arteriosclerosis with functional impairment following NO deprivation. The changes in MMPs and TIMP at the late stage (after 20 days) may be a compensatory response to prevent further renal damage. SN - 0304-4920 UR - https://www.unboundmedicine.com/medline/citation/18935914/Endothelin_and_gelatinases_in_renal_changes_following_blockade_of_nitric_oxide_synthase_in_hypertensive_rats_ L2 - https://medlineplus.gov/highbloodpressure.html DB - PRIME DP - Unbound Medicine ER -