PIOGLITAZONE ATTENUATES HYPERTENSION AND INHIBITS GROWTH OF RENAL ARTERIOLAR SMOOTH-MUSCLE IN RATS
PIOGLITAZONE ATTENUATES HYPERTENSION AND INHIBITS GROWTH OF RENAL ARTERIOLAR SMOOTH-MUSCLE IN RATS
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DOI：
10.1152/ajpregu.1993.265.4.r726
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发表时间：
1993-10-01
影响因子：
--
通讯作者：
KOTCHEN, TA
中科院分区：
文献类型：
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作者：
DUBEY, RK;ZHANG, HY;KOTCHEN, TA
高血压常常与胰岛素抵抗有关。我们评估了增加胰岛素敏感性的药物吡格列酮对Dahl盐敏感(Dahl-S)大鼠和一肾一夹SpragueDawley大鼠高血压发展的影响。我们还评价了吡格列酮对培养的肾小球前小动脉平滑肌细胞生长的影响。在饲喂3%氯化钠饲料的Dahl-S大鼠中，吡格列酮(20 mg/kg/d灌胃3wk)的尾部收缩压和直接动脉压低于对照组(n=10只/组)。在一肾一夹的SD大鼠中，服用吡格列酮的动物的收缩压也较低(P<；0.0001)。在体外，胰岛素、表皮生长因子(EGF)和胎牛血清(FCS)可促进小动脉平滑肌细胞的增殖(P<；0.01)，而吡格列酮(5um)可逆地抑制(P<；0.01)胰岛素、EGF和FCS诱导的细胞增殖。吡格列酮(0.01-100um)也浓度依赖性地抑制胰岛素(1mU/ml)、EGF(100 ng/ml)和5%FCS诱导的[H-3]胸腺嘧啶核苷掺入(P<；0.01)。因此，吡格列酮减轻了Dahl-S大鼠和一肾一夹大鼠的高血压发展。吡格列酮抑制血管平滑肌生长的能力可能与其降压作用有关。
Hypertension is frequently associated with insulin resistance. We evaluated the effects of pioglitazone, an agent that increases insulin sensitivity, on the development of hypertension in the Dahl salt-sensitive (Dahl-S) rat and in the one-kidney, one-clip Sprague-Dawley rat. We also evaluated the effects of pioglitazone on growth of cultured preglomerular renal arteriolar smooth muscle cells. In Dahl-S rats fed a 3% NaCl diet, tail systolic blood pressures and direct arterial pressures were lower (P < 0.05) in pioglitazone-treated (20 mg/kg daily by gavage for 3 wk) than in control rats (n = 10 rats/group). In one-kidney, one-clip Sprague-Dawley rats, systolic blood pressures were also lower in pioglitazone-treated animals (P < 0.0001). In vitro, proliferation of arteriolar smooth muscle cells was stimulated (P < 0.01) by insulin, epidermal growth factor (EGF), and fetal calf serum (FCS); pioglitazone (5 muM) reversibly inhibited (P < 0.01) insulin-, EGF-, and FCS-induced proliferation. Pioglitazone (0.01-100 muM) also inhibited insulin- (1 mU/ml), EGF- (100 ng/ml), and 5% FCS-induced [H-3]thymidine incorporation in a concentration-dependent manner (P < 0.01). Thus pioglitazone attenuated the development of hypertension in the Dahl-S rat and the one-kidney, one-clip rat. The ability of pioglitazone to inhibit growth of vascular smooth muscle may contribute to its hypotensive effect.