Kittikulsuth W, Hyndman K A, Pollock J S, Pollock D M
Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Physiol Res. 2018 Jun 27;67(Suppl 1):S149-S154. doi: 10.33549/physiolres.933858.
Renal medullary endothelin B receptors (ET(B)) mediate sodium excretion and blood pressure (BP) control. Several animal models of hypertension have impaired renal medullary ET(B) function. We found that 4-week high-caloric diet elevated systolic BP in Dahl salt-sensitive (Dahl S) rats (126+/-2 vs. 143+/-3 mm Hg, p<0.05). We hypothesized that renal medullary ET(B) function is dysfunctional in DS rats fed a high-caloric diet. We compared the diuretic and natriuretic response to intramedullary infusion of ET(B) agonist sarafotoxin 6c (S6c) in DS rats fed either a normal or high-caloric diet for 4 weeks. Urine was collected during intramedullary infusion of saline for baseline collection followed by intramedullary infusion of either saline or S6c. We first examined the ET(B) function in DS rats fed a normal diet. S6c increased urine flow (2.7+/-0.3 microl/min during baseline vs. 5.1+/-0.6 microl/min after S6c; p<0.05; n=5) and sodium excretion (0.28+/-0.05 vs. 0.81+/-0.17 micromol/min; p<0.05), suggesting that DS rats have renal medullary ET(B) function. However, DS rats fed a high-caloric diet displayed a significant increase in urine flow (2.7+/-0.4 vs. 4.2+/-0.4 microl/min, baseline vs. S6c infusion, respectively; p<0.05, n=6), but no significant change in sodium excretion in response to S6c (0.32+/-0.06 vs. 0.45+/-0.10 micromol/min). These data demonstrate that renal medullary ET(B) function is impaired in DS rats fed a high-caloric diet, which may be contributed to the elevation of blood pressure during high-caloric feeding in this model.
肾髓质内皮素B受体（ET(B)）介导钠排泄和血压控制。几种高血压动物模型的肾髓质ET(B)功能受损。我们发现，4周的高热量饮食使 Dahl 盐敏感（Dahl S）大鼠的收缩压升高（126±2 与 143±3 mmHg，p<0.05）。我们假设，高热量饮食喂养的DS大鼠肾髓质ET(B)功能存在障碍。我们比较了正常饮食或高热量饮食喂养4周的DS大鼠对髓内注射ET(B)激动剂沙拉新6c（S6c）的利尿和利钠反应。在髓内注射生理盐水以进行基线收集，随后髓内注射生理盐水或S6c期间收集尿液。我们首先检查了正常饮食喂养的DS大鼠的ET(B)功能。S6c增加了尿流（基线时为2.7±0.3微升/分钟，S6c注射后为5.1±0.6微升/分钟；p<0.05；n=5）和钠排泄（0.28±0.05与0.81±0.17微摩尔/分钟；p<0.05），表明DS大鼠具有肾髓质ET(B)功能。然而，高热量饮食喂养的DS大鼠尿流显著增加（分别为基线与S6c注射时2.7±0.4与4.2±0.4微升/分钟；p<0.05，n=6），但对S6c的钠排泄无显著变化（0.32±0.06与0.45±0.10微摩尔/分钟）。这些数据表明，高热量饮食喂养的DS大鼠肾髓质ET(B)功能受损，这可能导致该模型在高热量喂养期间血压升高。
