Renal endothelin system and excretory function in Wistar-Kyoto and Long-Evans rats

• Published in: Acta Physiologica Vol. 186; no. 1; pp. 67 - 76
• Main Authors: Girchev, R., Bäcker, A., Markova, P., Kramer, H. J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.01.2006; Blackwell
• Subjects: Animals; Biological and medical sciences; Blood Pressure - physiology; BQ-123; BQ-788; Electrolytes - urine; Endothelin A Receptor Antagonists; Endothelin B Receptor Antagonists; Endothelin-1 - analysis; Endothelin-1 - blood; Endothelins - physiology; Fundamental and applied biological sciences. Psychology; Glomerular Filtration Rate - physiology; Heart Rate - physiology; Infusions, Intravenous; Kidney - physiology; Kidney Cortex - chemistry; Long-Evans rat; Male; Oligopeptides - administration & dosage; Peptides, Cyclic - administration & dosage; Piperidines - administration & dosage; Rats; Rats, Inbred WKY; Rats, Long-Evans; Renal Circulation - physiology; renal endothelin; renal excretory function; RNA, Messenger - analysis; Urination - drug effects; Vertebrates: urinary system; Wistar-Kyoto rat; Excretion; Endothelin; Renal function; Rat; Hydroelectrolytic balance; Rodentia; Endothelin 1; renal endothelin; ETA endothelin receptor; Vertebrata; Mammalia; BQ-788; renal excretory function; Urinary system; Long-Evans rat; ETB endothelin receptor; Wistar-Kyoto rat; BQ-123
• ISSN: 1748-1708; 1748-1716
• DOI: 10.1111/j.1748-1716.2005.01501.x

Aim:  The role of the kidney endothelin system in the renal regulation of fluid and electrolyte excretion was investigated in Wistar–Kyoto (WKY) and Long–Evans (LE) rats in which we found previously marked differences in the renal excretory responses to endothelin A receptor blockade. Methods:  The selective endothelin A and B receptor antagonists BQ‐123 (16.4 nmol kg−1 min−1) and BQ‐788 (25 nmol kg−1 min−1) were infused i.v. for 50 min in conscious chronically instrumented WKY and LE rats and their renal function and renal endothelin system were studied. Results:  Without effects on glomerular filtration rate or renal blood flow, BQ‐123 and BQ‐788 decreased by more than 50% (P < 0.01) both urine flow rate and electrolyte excretion in WKY rats but only urine flow rate (P < 0.05) in LE rats. Endothelin‐1 content, preproET‐1/GPDH mRNA ratio, Bmax and Kd of total endothelin receptors in renal cortex did not differ between the two strains. In contrast, plasma endothelin‐1 concentration (0.58 ± 0.04 vs. 1.05 ± 0.01 femtomol mL−1; P < 0.01), renal papillary ET‐1 concentration (68 ± 5 vs. 478 ± 62 fmol mg−1 protein; P < 0.01) and preproET‐1/GPDH mRNA ratio (0.65 ± 0.09 vs. 0.88 ± 0.05; P < 0.05) as well as total endothelin receptor number in renal papilla (Bmax 5.3 ± 0.4 vs. and 9.0 ± 1.2 pmol mg−1 protein; P < 0.05) were markedly lower in LE than in WKY rats. In vitro studies showed that in both strains ETB receptors on renal cortical membranes amounted between 65% and 67% and on papillary membranes between 85% and 88%. Conclusion:  The present data show that the selective ETA or ETB receptor blockade differentially affects tubular water and salt handling, which becomes apparent in conditions of low renal papillary endothelin receptor number and tissue endothelin‐1 concentration.