Kassab S, Novak J, Miller T, Kirchner K, Granger J
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Hypertension. 1997 Sep;30(3 Pt 2):682-6. doi: 10.1161/01.hyp.30.3.682.
The aim of this study was to evaluate the role of endothelin (ET) in the hypertension associated with giving a high sodium diet in Dahl salt-sensitive (DS) rats. To achieve this goal, we examined the effects of intravenous infusion of the nonspecific ET(A)-ET(B) antagonist on arterial pressure and renal function in conscious, chronically instrumented DS and Dahl salt-resistant (DR) rats. After 3 weeks on a high sodium (8%) diet, mean arterial pressure (MAP) in DS rats (166+/-3 mm Hg) was significantly higher than in DR rats (124+/-3 mm Hg). Baseline glomerular filtration rate (GFR) and renal plasma flow (RPF) in DS rats (1.92+/-0.25 mL/min and 7.07+/-0.80 mL/min) were lower than in DR rats (2.52+/-0.21 mL/min and 7.98+/-0.85 mL/min), respectively. Renal vascular resistance was significantly higher in DS rats (32.78+/-5.88 mm Hg x mL(-1) x min(-1)) than in DR rats (24.60+/-5.04 mm Hg x mL(-1) x min(-1)). Intravenous infusion of the ET antagonist SB 209670 at a dose of 30 microg x kg(-1) x min(-1) for 75 minutes caused a significant decrease in MAP in DS rats (from 166+/-3 to 144+/-4 mm Hg). In contrast, the effect of the ET antagonism on MAP in DR rats was not significant. ET-antagonist infusion tended to improve GFR and RPF in DS but not in DR rats. To determine the renal effects of ET antagonism independent of the systemic hemodynamic responses, we examined the effects of the same ET antagonist in rats chronically implanted with a renal interstitial catheter. Arterial pressure in DS rats (181+/-5 mm Hg) was significantly higher than in DR rats (135+/-3 mm Hg). Renal interstitial infusion of SB 209670 at a dose of 200 ng x kg(-1) x min(-1) for 60 minutes caused no change in MAP in DS or DR rats. Intrarenal ET antagonism significantly increased GFR (25%), RPF (30%), urine flow (32%), and urinary sodium excretion (25%) in DS rats, while it had no significant effect in DR rats. Fractional excretion of sodium was not significantly changed by renal interstitial infusion of the ET antagonist in DS rats, indicating that improved renal excretory function in DS rats is most likely due to the associated improvement in renal hemodynamics. We conclude that ET may play a role in the attenuated renal hemodynamics and possibly the development of Dahl salt-sensitive hypertension.
本研究的目的是评估内皮素（ET）在给予高钠饮食的 Dahl 盐敏感（DS）大鼠所患高血压中的作用。为实现这一目标，我们检测了静脉输注非特异性 ET(A)-ET(B)拮抗剂对清醒、长期植入仪器的 DS 大鼠和 Dahl 盐抵抗（DR）大鼠动脉血压和肾功能的影响。在高钠（8%）饮食 3 周后，DS 大鼠的平均动脉压（MAP）（166±3 mmHg）显著高于 DR 大鼠（124±3 mmHg）。DS 大鼠的基线肾小球滤过率（GFR）和肾血浆流量（RPF）（分别为 1.92±0.25 mL/min 和 7.07±0.80 mL/min）低于 DR 大鼠（分别为 2.52±0.21 mL/min 和 7.98±0.85 mL/min）。DS 大鼠的肾血管阻力（32.78±5.88 mmHg·mL⁻¹·min⁻¹）显著高于 DR 大鼠（24.60±5.04 mmHg·mL⁻¹·min⁻¹）。以 30 μg·kg⁻¹·min⁻¹ 的剂量静脉输注 ET 拮抗剂 SB 209670 75 分钟，导致 DS 大鼠的 MAP 显著降低（从 166±3 降至 144±4 mmHg）。相比之下，ET 拮抗对 DR 大鼠 MAP 的影响不显著。ET 拮抗剂输注倾向于改善 DS 大鼠的 GFR 和 RPF，但对 DR 大鼠无此作用。为了确定独立于全身血流动力学反应的 ET 拮抗对肾脏的影响，我们检测了相同的 ET 拮抗剂对长期植入肾间质导管的大鼠的影响。DS 大鼠的动脉血压（181±5 mmHg）显著高于 DR 大鼠（135±3 mmHg）。以 200 ng·kg⁻¹·min⁻¹ 的剂量肾间质输注 SB 209670 60 分钟，DS 大鼠或 DR 大鼠的 MAP 均未发生变化。肾内 ET 拮抗使 DS 大鼠的 GFR（25%）、RPF（30%）、尿流量（32%）和尿钠排泄（25%）显著增加，而对 DR 大鼠无显著影响。肾间质输注 ET 拮抗剂后，DS 大鼠的钠排泄分数无显著变化，这表明 DS 大鼠肾排泄功能的改善很可能是由于肾血流动力学的相关改善。我们得出结论，ET 可能在 Dahl 盐敏感型高血压的肾血流动力学减弱及可能的发病过程中起作用。
