Key result
Extrarenal ET(B) receptors limit salt-sensitivity in rats, preventing severe hypertension and renal dysfunction on a high-sodium diet.
Extrarenal ET(B) receptors play a crucial role in limiting salt-sensitive hypertension, likely by functioning as a clearance receptor for ET1.
No immediate clinical implications for hypertension; extends preclinical models of extrarenal ET(B) function in salt sensitivity.
Endothelin-B receptor (ET(B))-deficient rats have low-renin, salt-sensitive hypertension. We hypothesized this was caused by an absence of renal ET(B) 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 ET(B)-deficient rats. We found that ET(B) 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 (ET(A)) mRNA, however, are similarly increased by dietary Na in ET(B)-WT and ET(B)-deficient rats. We then determined the effect of chronic ET(A) blockade on blood pressure (direct conscious measurements), urinary protein excretion, and creatinine clearance (Crcl). On a Na-deficient diet, ET(B)-deficient rats have mild proteinuria and impaired Crcl. On a high-Na diet, severe hypertension and renal dysfunction develop in ET(B)-deficient rats. Chronic ET(A) 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 ET(B) deficiency in the body is associated with renal injury and an impaired ability to excrete an Na load. We also found that ET(B) deficiency in the body affects blood pressure response to dietary Na. Expression of ET1 and ET(A) are regulated by dietary Na. ET(B) receptors outside of the kidney, likely by functioning as a clearance receptor for ET1, limit salt-sensitivity in rats.
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Ohkita et al. (2005) studied Salt-sensitive hypertension. High dietary sodium and ET(A) blockade vs. Na-deficient diet and Wild-type rats was evaluated on Blood pressure, urinary protein excretion, and creatinine clearance. Extrarenal ET(B) receptors limit salt-sensitivity in rats, preventing severe hypertension and renal dysfunction on a high-sodium diet.
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