Extrarenal ETB plays a significant role in controlling cardiovascular responses to high dietary sodium in rats

Mamoru Ohkita, Yuqin Wang, Ngoc Diep T Nguyen, Yu Hwai Tsai, S. Clay Williams, Richard C. Wiseman, Paul D. Killen, Shujun Li, Masashi Yanagisawa, Cheryl E. Gariepy

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Endothelin-B receptor (ETB)-deficient rats have low-renin, salt-sensitive hypertension. We hypothesized this was caused by an absence of renal ETB signaling and performed a series of experiments to examine the effect of dietary sodium (Na) on endothelin-1 (ET1) expression and renal function in wild-type (WT) and ETB-deficient rats. We found that ETB deficiency, but not dietary Na, increases circulating and tissue (kidney and aorta) ET1 levels. Quantitative reverse-transcription polymerase chain reaction reveals that aortic and renal ET1 and endothelin-A receptor (ETA) mRNA, however, are similarly increased by dietary Na in ET B-WT and ETB-deficient rats. We then determined the effect of chronic ETA blockade on blood pressure (direct conscious measurements), urinary protein excretion, and creatinine clearance (Crcl). On a Na-deficient diet, ETB-deficient rats have mild proteinuria and impaired Crcl. On a high-Na diet, severe hypertension and renal dysfunction develop in ETB-deficient rats. Chronic ETA blockade prevents hypertension and renal injury. To determine the role of the renal versus the extrarenal endothelin system, we performed renal cross- transplantation. We found that ETB deficiency in the body is associated with renal injury and an impaired ability to excrete an Na load. We also found that ETB deficiency in the body affects blood pressure response to dietary Na. Expression of ET1 and ETA are regulated by dietary Na. ETB receptors outside of the kidney, likely by functioning as a clearance receptor for ET1, limit salt-sensitivity in rats.

Original languageEnglish (US)
Pages (from-to)940-946
Number of pages7
JournalHypertension
Volume45
Issue number5
DOIs
StatePublished - May 1 2005

Keywords

  • Endothelin
  • Natriuresis
  • Proteinuria
  • Sympathetic nervous system
  • Transplantation

ASJC Scopus subject areas

  • Internal Medicine

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    Ohkita, M., Wang, Y., Nguyen, N. D. T., Tsai, Y. H., Williams, S. C., Wiseman, R. C., Killen, P. D., Li, S., Yanagisawa, M., & Gariepy, C. E. (2005). Extrarenal ETB plays a significant role in controlling cardiovascular responses to high dietary sodium in rats. Hypertension, 45(5), 940-946. https://doi.org/10.1161/01.HYP.0000161878.81141.62