Bryan K Becker, Caroline M Grady, Alexa E Markl, Alfredo A Torres Rodriguez, David M Pollock
{"title":"内皮素 B 受体缺乏症大鼠模型中肾传入神经活动升高。","authors":"Bryan K Becker, Caroline M Grady, Alexa E Markl, Alfredo A Torres Rodriguez, David M Pollock","doi":"10.1152/ajprenal.00064.2023","DOIUrl":null,"url":null,"abstract":"<p><p>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<sub>B</sub>) receptor activation. We hypothesized that ET<sub>B</sub>-deficient (ET<sub>B</sub>-def) rats, which are devoid of functional ET<sub>B</sub> 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<sub>B</sub>-def animals lack a response to a physiological stimulus, prostaglandin E<sub>2</sub>, compared with transgenic controls but respond equally to a noxious stimulus, capsaicin. Surprisingly, we observed elevated renal afferent nerve activity in intact ET<sub>B</sub>-def rats compared with transgenic controls under both normal- and high-salt diets. ET<sub>B</sub>-def rats have been previously shown to have heightened global sympathetic tone, and we also observed higher total renal sympathetic nerve activity in ET<sub>B</sub>-def rats compared with transgenic controls under both normal- and high-salt diets. These data indicate that ET<sub>B</sub> receptors are integral mediators of the sympathoinhibitory renal afferent reflex (renorenal reflex), and, in a genetic rat model of ET<sub>B</sub> deficiency, the preponderance of sympathoexcitatory renal afferent nerve activity prevails and may contribute to hypertension.<b>NEW & NOTEWORTHY</b> 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.</p>","PeriodicalId":7588,"journal":{"name":"American Journal of Physiology-renal Physiology","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10396274/pdf/","citationCount":"0","resultStr":"{\"title\":\"Elevated renal afferent nerve activity in a rat model of endothelin B receptor deficiency.\",\"authors\":\"Bryan K Becker, Caroline M Grady, Alexa E Markl, Alfredo A Torres Rodriguez, David M Pollock\",\"doi\":\"10.1152/ajprenal.00064.2023\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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<sub>B</sub>) receptor activation. We hypothesized that ET<sub>B</sub>-deficient (ET<sub>B</sub>-def) rats, which are devoid of functional ET<sub>B</sub> 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<sub>B</sub>-def animals lack a response to a physiological stimulus, prostaglandin E<sub>2</sub>, compared with transgenic controls but respond equally to a noxious stimulus, capsaicin. Surprisingly, we observed elevated renal afferent nerve activity in intact ET<sub>B</sub>-def rats compared with transgenic controls under both normal- and high-salt diets. ET<sub>B</sub>-def rats have been previously shown to have heightened global sympathetic tone, and we also observed higher total renal sympathetic nerve activity in ET<sub>B</sub>-def rats compared with transgenic controls under both normal- and high-salt diets. These data indicate that ET<sub>B</sub> receptors are integral mediators of the sympathoinhibitory renal afferent reflex (renorenal reflex), and, in a genetic rat model of ET<sub>B</sub> deficiency, the preponderance of sympathoexcitatory renal afferent nerve activity prevails and may contribute to hypertension.<b>NEW & NOTEWORTHY</b> Here, we found that endothelin B receptors are an important contributor to renal afferent nerve responsiveness to a high-salt diet. 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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 (ETB) receptor activation. We hypothesized that ETB-deficient (ETB-def) rats, which are devoid of functional ETB 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 ETB-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 ETB-def rats compared with transgenic controls under both normal- and high-salt diets. ETB-def rats have been previously shown to have heightened global sympathetic tone, and we also observed higher total renal sympathetic nerve activity in ETB-def rats compared with transgenic controls under both normal- and high-salt diets. These data indicate that ETB receptors are integral mediators of the sympathoinhibitory renal afferent reflex (renorenal reflex), and, in a genetic rat model of ETB 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.
期刊介绍:
The American Journal of Physiology - Renal Physiology publishes original manuscripts on timely topics in both basic science and clinical research. Published articles address a broad range of subjects relating to the kidney and urinary tract, and may involve human or animal models, individual cell types, and isolated membrane systems. Also covered are the pathophysiological basis of renal disease processes, regulation of body fluids, and clinical research that provides mechanistic insights. Studies of renal function may be conducted using a wide range of approaches, such as biochemistry, immunology, genetics, mathematical modeling, molecular biology, as well as physiological and clinical methodologies.