Elevated renal afferent nerve activity in a rat model of endothelin B receptor deficiency

Renal nerves have been an attractive target for interventions aimed at lowering blood pressure; however, the specific roles of renal afferent (sensory) versus efferent sympathetic nerves in mediating hypertension are poorly characterized. A number of studies have suggested that a sympathoexcitatory signal conveyed by renal afferents elicits increases in blood pressure, whereas other studies identified sympathoinhibitory afferent pathways. These sympathoinhibitory pathways have been identified as protective against salt-sensitive increases in blood pressure through endothelin B (ET_B) receptor activation. We hypothesized that ET_B-deficient (ET_B-def) rats, which are devoid of functional ET_B receptors except in adrenergic tissues, lack appropriate sympathoinhibition and have lower renal afferent nerve activity following a high-salt diet compared with transgenic controls. We found that isolated renal pelvises from high salt-fed ET_B-def animals lack a response to a physiological stimulus, prostaglandin E₂, compared with transgenic controls but respond equally to a noxious stimulus, capsaicin. Surprisingly, we observed elevated renal afferent nerve activity in intact ET_B-def rats compared with transgenic controls under both normal- and high-salt diets. ET_B-def rats have been previously shown to have heightened global sympathetic tone, and we also observed higher total renal sympathetic nerve activity in ET_B-def rats compared with transgenic controls under both normal- and high-salt diets. These data indicate that ET_B receptors are integral mediators of the sympathoinhibitory renal afferent reflex (renorenal reflex), and, in a genetic rat model of ET_B deficiency, the preponderance of sympathoexcitatory renal afferent nerve activity prevails and may contribute to hypertension.NEW & NOTEWORTHY Here, we found that endothelin B receptors are an important contributor to renal afferent nerve responsiveness to a high-salt diet. Rats lacking endothelin B receptors have increased afferent nerve activity that is not responsive to a high-salt diet.