Low NaCl intake elevates renal medullary endothelin‐1 and endothelin A (ETA) receptor mRNA but not the sensitivity of renal Na⁺ excretion to ETA receptor blockade in rats

Sep 26, 2007Acta physiologica (Oxford, England)

Low salt intake increases certain kidney signals but does not change how the kidney responds to blocking one receptor in rats

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Abstract

Medullary ET-1 content was 983 +/- 88 ng mg(-1) protein in rats on 0.15% NaCl compared to 479 +/- 42 ng mg(-1) protein in those on 1.80% NaCl.

Pre-pro-endothelin-1, endothelin A, and endothelin B receptor mRNA levels were 50%, 81%, and 33% higher, respectively, in rats on 0.15% NaCl compared to those on 1.80% NaCl.
Losartan treatment decreased medullary gene expression in rats consuming 0.15% NaCl.
Chronic treatment with an endothelin A receptor blocker lowered arterial pressure by 8-10 mmHg in rats on 0.15% NaCl without changing renal sodium balances.
Acute blockade of endothelin A or B receptors did not affect medullary blood flow or fractional sodium excretion in either dietary group.
Renal medullary ET-1 content and mRNA expression of endothelin system components may be inversely related to NaCl intake.

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AIMS: This study was performed to investigate the effects of NaCl intake on renal mRNA expression of pre-pro-endothelin-1 (ET-1), endothelin A (ET(A)) and endothelin B (ET(B)) receptors as well as on renal ET-1 content in rats. We further tested for NaCl intake-dependent differences in the contribution of the ET system to renal sodium handling.

METHODS: Male Sprague-Dawley rats with telemetric devices were randomized to 0.15%, 0.60% and 1.80% NaCl diets with or without losartan. Renal sodium balance and arterial pressure were monitored. Renal blood flow and fractional sodium excretion (FENa) were measured in response to acute infusion of ET(A) and ET(B) blockers into the inner stripe of the outer renal medulla.

RESULTS: Medullary pre-pro-ET-1, ET(A) and ET(B) receptor mRNA was 50%, 81% and 33% higher in rats on 0.15% vs. 1.80% NaCl. Losartan reduced medullary gene expression in rats on 0.15% NaCl. Medullary ET-1 content was 983 +/- 88 and 479 +/- 42 ng mg(-1) protein in rats on 0.15% and 1.80% NaCl (P < 0.001). Chronic ET(A) receptor blocker treatment reduced arterial pressure by 8-10 mmHg in rats on 0.15% vs. 1.80% NaCl without affecting renal sodium balances. Acute medullary ET(A) or ET(B) receptor blockade did not alter medullary blood flow and FENa in animals on either diet.

CONCLUSION: In rats renal medullary ET-1 content and mRNA expression of three ET system components are inversely related to NaCl intake. Higher expression levels on low NaCl intake are AT(1) receptor dependent but are not associated with increased sensitivity of renal sodium handling to ET(A) receptor blockade.

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Low NaCl intake elevates renal medullary endothelin‐1 and endothelin A (ETA) receptor mRNA but not the sensitivity of renal Na⁺ excretion to ETA receptor blockade in rats

Abstract

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