Vascular dilatatory responses to sodium nitroprusside (SNP) and alpha-adrenergic antagonism in female and male normal and diabetic rats.

B. Martínez-Nieves, Joseph C. Dunbar
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引用次数: 24

Abstract

Diabetes is associated with impaired vascular dilatatory responses that appear to be influenced by sex as well as diabetic state. Therefore, we hypothesized that vascular and sympathetic control function exhibit a greater deterioration following the induction of diabetes in female than in male rats. We conducted a comparative determination of the effect of sodium nitroprusside (SNP, a nitrous oxide donor) and that of an alpha1-adrenergic antagonist, prazosin, on selective vascular flows, mean arterial pressure (MAP), and heart rate (HR), in female and male normal and diabetic rats. Rats were made diabetic using streptozotocin (50 mg/kg, iv) and maintained for 5-6 weeks. Following anesthesia with urethane/alpha-chloralose, the femoral artery and vein were cannulated for recording and sampling. Flow probes were placed on the iliac, renal, and superior mesenteric arteries. SNP (1, 5, 10, and 20 microg/kg) infusions resulted in a dose-dependent decrease in MAP in normal and diabetic rats. The decrease in MAP in normal males was 37% less at the 20 microg/kg concentration of SNP when compared to normal females. The HR was not significantly changed in response to the hypotensive effect of SNP; however, reflex tachycardia was more prominent in diabetic males. The vascular conductance (flow/MAP) was increased by SNP in normal and diabetic rats in a dose-dependent fashion; however, the responsiveness was decreased in the iliac and superior mesenteric and increased in the renal arteries in diabetics when compared to normals. Diabetic males were 42% and 28% less responsive to SNP in the iliac and superior mesenteric arteries, respectively. On the other hand, diabetic females were 1.5-fold more responsive in the renal artery when compared to normals. Prazosin (4 mg/kg) decreased the MAP in normal and diabetic rats to a comparable degree. Prazosin increased the vascular conductance in all three vascular beds in normal and diabetic rats with the greater increase occurring in the iliac (118%) and superior mesenteric (110%) arteries. We concluded that diabetes is associated with an increased response to NO in the renal vessels and a decreased response in the iliac and superior mesenteric vessels in both females and males. alpha-Adrenergic tone was greatest in diabetic female and male rats. This study suggests that decreased vascular flow in diabetes is a result of a combination of decreased sensitivity to NO and increased adrenergic tone.
硝普钠(SNP)和α -肾上腺素能拮抗剂对雌雄正常及糖尿病大鼠血管扩张的影响。
糖尿病与血管扩张反应受损有关,这似乎受性别和糖尿病状态的影响。因此,我们假设雌性大鼠的血管和交感神经控制功能在诱导糖尿病后表现出比雄性大鼠更大的恶化。我们比较了硝普钠(SNP,一种氧化亚氮供体)和α - 1肾上腺素能拮抗剂吡唑嗪对雌性和雄性正常大鼠和糖尿病大鼠的选择性血管流动、平均动脉压(MAP)和心率(HR)的影响。采用链脲佐菌素(50 mg/kg,静脉滴注)致大鼠糖尿病,维持5 ~ 6周。经氨基甲酸乙酯/ -氯氯蔗糖麻醉后,留置股动脉和股静脉进行记录和取样。血流探头放置在髂动脉、肾动脉和肠系膜上动脉。SNP(1、5、10和20微克/千克)输注导致正常和糖尿病大鼠MAP呈剂量依赖性下降。与正常女性相比,当SNP浓度为20微克/千克时,正常男性的MAP减少了37%。SNP的降压作用对HR没有显著影响;然而,反射性心动过速在糖尿病男性中更为突出。SNP使正常大鼠和糖尿病大鼠血管导度(flow/MAP)呈剂量依赖性增加;然而,与正常人相比,糖尿病患者的髂动脉和肠系膜上动脉的反应性降低,肾动脉的反应性升高。糖尿病男性对髂动脉和肠系膜上动脉SNP的反应分别降低42%和28%。另一方面,女性糖尿病患者的肾动脉反应是正常人的1.5倍。吡唑嗪(4mg /kg)对正常大鼠和糖尿病大鼠的MAP均有相当程度的降低。吡唑嗪增加了正常大鼠和糖尿病大鼠所有三个血管床的血管传导,其中髂动脉(118%)和肠系膜上动脉(110%)的血管传导增加最多。我们得出的结论是,糖尿病与肾血管对NO的反应增加和髂血管和肠系膜上血管的反应减少有关。α -肾上腺素能张力在糖尿病雌性和雄性大鼠中最高。本研究提示糖尿病患者血管血流减少是一氧化氮敏感性降低和肾上腺素能张力增加的结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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