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Function and expression of endothelin receptor subtypes in the kidneys of spontaneously hypertensive rats.
Cardiovasc Res. 1996 Apr; 31(4):499-510.CR

Abstract

OBJECTIVE

The renal endothelin system has been implicated in the development and maintenance of hypertension in spontaneously hypertensive rats (SHR). However, little is known about the function and cellular distribution of endothelin receptor subtypes in the kidneys of SHR.

METHODS

We analyzed the expression of endothelin receptor subtypes in the kidneys of 16-week-old SHR using Scatchard analysis, receptor autoradiography, Northern blot analysis and in situ hybridization. Wistar-Kyoto rats (WKY) served as controls. Furthermore, we investigated the effects of the mixed (A/B) endothelin receptor antagonist bosentan and the ETA receptor antagonist BQ 123 on mean arterial blood pressure (MAP), renal blood flow (RBF) and glomerular filtration rate (GFR) in conscious chronically instrumented rats.

RESULTS

In SHR, we found by receptor autoradiography an overexpression of the endothelin A receptor (ETA) in the glomeruli (2.2 +/- 0.4-fold; P < 0.05) and smooth muscle cells of intrarenal arteries (1.9 +/- 0.2-fold; P < 0.05) compared to age-matched WKY. In addition, our study revealed a pronounced upregulation of endothelin B receptor (ETB) in the glomeruli of SHR (5.6 +/- 0.8-fold; P < 0.01). Blockade of endothelin receptors in SHR with bosentan (A and B receptor blockade) as well as with BQ 123 (A receptor blockade) led to a significant decrease in MAP (-18.6 +/- 2.1 and -19 +/- 1.3 mmHg, respectively; P < 0.05 in both cases) and a significant increase in RBF (+2.8 +/- 0.5 and +3.1 +/- 0.37 ml/min, respectively; P < 0.05 in both cases). The blockade of both ETA and ETB by bosentan had no further effect on MAP reduction or RBF increase in SHR compared to the ETA blockade by BQ 123. The ETA antagonist BQ 123 had no effect on GFR either in SHR or in WKY, whereas the combined blockade of ETA and ETB by bosentan significantly decreased GFR in SHR by about 50% but not in WKY.

CONCLUSIONS

Our data demonstrated a correlation between the overexpression of vascular ETA receptors and the pronounced upregulation of glomerular ETB receptors in the kidneys of SHR and their impact on the regulation of renal blood flow, glomerular filtration rate and blood pressure in these animals.

Authors+Show Affiliations

Department of Nephrology, Universitätsklinikum Charité der Humboldt Universität zu Berlin, City, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

8689641

Citation

Hocher, B, et al. "Function and Expression of Endothelin Receptor Subtypes in the Kidneys of Spontaneously Hypertensive Rats." Cardiovascular Research, vol. 31, no. 4, 1996, pp. 499-510.
Hocher B, Rohmeiss P, Zart R, et al. Function and expression of endothelin receptor subtypes in the kidneys of spontaneously hypertensive rats. Cardiovasc Res. 1996;31(4):499-510.
Hocher, B., Rohmeiss, P., Zart, R., Diekmann, F., Vogt, V., Metz, D., Fakhury, M., Gretz, N., Bauer, C., Koppenhagen, K., Neumayer, H. H., & Distler, A. (1996). Function and expression of endothelin receptor subtypes in the kidneys of spontaneously hypertensive rats. Cardiovascular Research, 31(4), 499-510.
Hocher B, et al. Function and Expression of Endothelin Receptor Subtypes in the Kidneys of Spontaneously Hypertensive Rats. Cardiovasc Res. 1996;31(4):499-510. PubMed PMID: 8689641.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Function and expression of endothelin receptor subtypes in the kidneys of spontaneously hypertensive rats. AU - Hocher,B, AU - Rohmeiss,P, AU - Zart,R, AU - Diekmann,F, AU - Vogt,V, AU - Metz,D, AU - Fakhury,M, AU - Gretz,N, AU - Bauer,C, AU - Koppenhagen,K, AU - Neumayer,H H, AU - Distler,A, PY - 1996/4/1/pubmed PY - 1996/4/1/medline PY - 1996/4/1/entrez SP - 499 EP - 510 JF - Cardiovascular research JO - Cardiovasc. Res. VL - 31 IS - 4 N2 - OBJECTIVE: The renal endothelin system has been implicated in the development and maintenance of hypertension in spontaneously hypertensive rats (SHR). However, little is known about the function and cellular distribution of endothelin receptor subtypes in the kidneys of SHR. METHODS: We analyzed the expression of endothelin receptor subtypes in the kidneys of 16-week-old SHR using Scatchard analysis, receptor autoradiography, Northern blot analysis and in situ hybridization. Wistar-Kyoto rats (WKY) served as controls. Furthermore, we investigated the effects of the mixed (A/B) endothelin receptor antagonist bosentan and the ETA receptor antagonist BQ 123 on mean arterial blood pressure (MAP), renal blood flow (RBF) and glomerular filtration rate (GFR) in conscious chronically instrumented rats. RESULTS: In SHR, we found by receptor autoradiography an overexpression of the endothelin A receptor (ETA) in the glomeruli (2.2 +/- 0.4-fold; P < 0.05) and smooth muscle cells of intrarenal arteries (1.9 +/- 0.2-fold; P < 0.05) compared to age-matched WKY. In addition, our study revealed a pronounced upregulation of endothelin B receptor (ETB) in the glomeruli of SHR (5.6 +/- 0.8-fold; P < 0.01). Blockade of endothelin receptors in SHR with bosentan (A and B receptor blockade) as well as with BQ 123 (A receptor blockade) led to a significant decrease in MAP (-18.6 +/- 2.1 and -19 +/- 1.3 mmHg, respectively; P < 0.05 in both cases) and a significant increase in RBF (+2.8 +/- 0.5 and +3.1 +/- 0.37 ml/min, respectively; P < 0.05 in both cases). The blockade of both ETA and ETB by bosentan had no further effect on MAP reduction or RBF increase in SHR compared to the ETA blockade by BQ 123. The ETA antagonist BQ 123 had no effect on GFR either in SHR or in WKY, whereas the combined blockade of ETA and ETB by bosentan significantly decreased GFR in SHR by about 50% but not in WKY. CONCLUSIONS: Our data demonstrated a correlation between the overexpression of vascular ETA receptors and the pronounced upregulation of glomerular ETB receptors in the kidneys of SHR and their impact on the regulation of renal blood flow, glomerular filtration rate and blood pressure in these animals. SN - 0008-6363 UR - https://www.unboundmedicine.com/medline/citation/8689641/Function_and_expression_of_endothelin_receptor_subtypes_in_the_kidneys_of_spontaneously_hypertensive_rats_ L2 - https://medlineplus.gov/highbloodpressure.html DB - PRIME DP - Unbound Medicine ER -