ET B Receptors in High Salt Diet‐Induced Decline of Renal Autoregulation in Rats

Abstract

High salt (HS) diet is linked to increased endothelin-1 (ET-1) and salt-dependent hypertension. Previous studies showed that HS treatment increased renal microvascular ETB receptor expression and impaired renal blood flow (RBF) autoregulation. We hypothesized that HS leads to a decline of renal autoregulation via activation of ETB receptors. RBF autoregulation was assessed in anesthetized ETB deficient (ETB) and intact control littermates (Con) rats fed normal salt (NS) or HS (8% NaCl) for 2 weeks. RBF was monitored using an ultrasonic flow probe and autoregulation was assessed during step-decrements of arterial pressure imposed using an aortic occluder placed between the two renal arteries. ETB deficient rats (n=6) exhibited significantly elevated baseline mean arterial pressure (MAP, 132±5 vs. 116±1 mmHg in Con+NS, n=8, P<0.05). HS did not change MAP in either group but significantly increased RBF in Con rats (n=8, 12.5±0.7 vs. 9.2±0.5 ml/min.gkw in Con+NS, P<0.05) while decreasing RBF in ETB rats (6.8±0.6 ml/min.gkw vs. Con+NS, P<0.05). HS led to attenuated autoregulation of RBF in Con rats. Decreasing renal perfusion pressure from ambient to 95 mmHg resulted in an 11±2% decrease in RBF in Con+HS versus a 3±1% in Con+NS (P<0.05). Accordingly, autoregulatory index (AI) was 0.63±0.08 in Con+HS versus 0.18±0.09 in Con+NS (P<0.05). In contrast, RBF remained fairly stable in ETB+NS and ETB+HS rats during a stepwise reduction of renal perfusion pressure from ambient to 95 mmHg. AI averaged 0.26±0.14 and 0.12±0.24, respectively, suggesting intact autoregulation in ETB deficient rats. These data suggest that HS leads to attenuated RBF autoregulation and increased RBF via ETB receptoractivation.