地龙降压蛋白对自发性高血压大鼠降压作用及其机制的影响

目的:初步探讨地龙降压蛋白对自发性高血压大鼠(spontaneously hypertension rat,SHR)的降压作用及机制。方法:选择16周龄雄性SHR 24只随机分为3组:模型组、地龙降压蛋白低剂量组、地龙降压蛋白高剂量组,另纳入8只同龄雄性Wistar大鼠为正常对照组,干预持续28d。采用无创尾动脉套袖法观察地龙降压蛋白对SHR的降压作用;放射免疫分析法测定SHR血浆、肾脏局部醛固酮(aldosterone,Ald)、6-酮-前列腺素-F1α(6-Keto-PGF1α)含量。结果:地龙降压蛋白低、高剂量组均可明显降低SHR的血压,与模型组比较有显著性差异(P<0.05),可明显降低SHR血浆、肾脏Ald的水平(P<0.05);同时显著升高血浆、肾脏局部6-Keto-PGF1α的含量(P<0.05)。结论:地龙降压蛋白对SHR有降压作用,其降压机制可能与降低SHR血浆、肾脏Ald的水平,升高血浆、肾脏局部6-Keto-PGF1α的含量有关。     

Solid dispersion of rutaecarpine improved its antihypertensive effect in spontaneously hypertensive rats

It was reported previously that rutaecarpine produced a hypotensive effect in phenol‐induced and 2‐kidney, 1‐clip hypertensive rats. However, the same dose of crude rutaecarpine did not produce significant hypotensive effects when applied to spontaneously hypertensive rats (SHR). In the present study, a different dose of rutaecarpine solid dispersion was administered intragastrically to SHR. The systolic blood pressure was monitored by the tail‐cuff method with an electro‐sphygmomanometer. The plasma concentration of rutaecarpine, calcitonin gene‐related peptide (CGRP) and the mRNA levels of CGRP in dorsal root ganglion were determined. The results showed that administration of the solid dispersion significantly increased the blood concentration of rutaecarpine, accompanied by significant hypotensive effects in SHR in a dose‐dependent manner. The levels of plasma CGRP were also elevated significantly, concomitantly with the increased mRNA levels in the dorsal root ganglion in a dose‐dependent manner. It was concluded that a change of the dosage from the crude drug to solid dispersion could improve significantly the efficiency of rutaecarpine absorption and increase its plasma concentration. The anti‐hypertensive effect exerted by rutaecarpine solid dispersion in SHR is mediated by CGRP. Copyright © 2008 John Wiley & Sons, Ltd.     

降压益肾颗粒对SHR循环及肾脏局部 AngⅡ、ET的影响

目的:观察降压益肾颗粒对SHR循环及肾脏局部AngⅡ、ET的影响。方法:将SHR随机分为降压益肾大、小剂量组、尼群地平对照组、生理盐水组。治疗8周后处死,取肾脏,放免法测定AngⅡ、ET。结果:降压益肾颗粒能明显降低循环及肾脏局部AngⅡ、ET,作用优于尼群地平组,P<0.05。结论:降压益肾颗粒通过降低循环及肾脏中AngⅡ、ET对SHR大鼠肾脏产生保护作用。     

Comparison of catecholamine release in the isolated adrenal glands of SHR and WKY rats

1 The present study was designed to investigate the secretion of catecholamines (CA) evoked by stimulation of cholinergic receptors and membrane depolarization from the isolated perfused adrenal gland of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKYR) at adult age. 2 The wet weight of adrenal gland in SHR was greater than that in WKYR. The CA releasing responses evoked by acetylcholine (5.32 x 10-3 m), and high potassium (5.6 x 10-2 m), a membrane depolarizer, were significantly lower in WKYR than in SHR. 3 The secretory responses of CA evoked by DMPP (10-4 m for 2 min), a selective agonist of neuronal nicotinic receptors, and McN-A-343 (10-4 m for 2 min), a selective agonist of neuronal muscarinic receptors, were also significantly lower in WKYR than in SHR. 4 The CA release evoked by Bay-K-8644 (10-5 m), a dihydropyridine-sensitive Ca2+ channel activator, and cyclopiazonic acid (10-5 m), a selective inhibitor of Ca2+-ATPase in the endoplasmic reticulum, were also significantly greater in SHR than WKYR. 5 Taken together, these experimental results demonstrate that the CA secretion evoked by stimulation of cholinergic (nicotinic and muscarinic) receptors as well as membrane depolarization is enhanced more greatly in the perfused adrenal glands of SHR than in those of WKYR. It is suggested that the augmented CA release in SHR compared with WKYR was involved in essential hypertensive pathogenesis.     

Effect of phenylephrine injected into the nucleus tractus solitarius of Sprague-Dawley rats and spontaneously hypertensive rats

In alpha-chloralose-anesthetized Sprague-Dawley (SD) rats with unilateral nucleus tractus solitarius (NTS) lesions, injection of the alpha(1)-adrenergic receptor agonist phenylephrine into the contralateral NTS dose-dependently increased arterial pressure (AP). Bunazosin (0.1 nmol) or prazosin (0.36 nmol), an alpha(1)-adrenergic receptor antagonist, also increased AP. When injected into the NTS, pre-treatment with phenylephrine (10 nmol) or both antagonists abolished the cardiovascular effects of glutamate and acetylcholine. In contrast, pre-treatment with prazosin or methylatropine did not alter the effect of phenylephrine. Phenylephrine (30 nmol) injected into the NTS abolished aortic depressor nerve (ADN) evoked-responses. The pressor effect of phenylephrine in the NTS was exaggerated in spontaneously hypertensive rats (SHR). These results suggest that when injected into the NTS, the effect of phenylephrine may be due to a baroreflex blockade resulting from direct modulatory actions or non-specific neuronal alterations rather than stimulating the alpha(1)-adrenergic receptor. Additionally, this effect is enhanced in SHR.     

注意缺陷多动障碍模型大鼠注意定势转移能力的行为学评价

目的了解注意缺陷多动障碍动物模型幼年自发性高血压大鼠(SHR)注意定势转移能力。方法雄性鼠龄21d的SHR(n=6),对照组WKY(n=6)。大鼠适应10d,完成在点食碗中寻找食物作为奖赏物的行为训练。观察指标:潜伏期;大鼠连续6次正确完成参数的循环数和总时间。结果SHR和WKY大鼠仅在Edshift阶段潜伏期分别为(3.5±2.35)s和(13±8.74)s,差异有显著性(P<0.05)。所有阶段SHR能够连续6次正确完成操作任务所需要的循环次数明显多于WKY大鼠,差异有显著性(P<0.05~0.01)。SHR完成SD与Edshift阶段所需要的循环数分别为(17.33±4.84)次和(12.67±3.50)次,两者存在高度相关(r=0.833,P=0.039);WKY完成SD与Edshift阶段所需要的循环数分别为(8.0±1.41)次和(6.67±1.21)次,两者无显著性相关(r=0.234,P=0.656)。SHR仅在CD和CDR阶段所需要的总时间长于WKY大鼠(P<0.05)。结论幼年大鼠可以完成注意定势转移能力的评定,幼年SHR大鼠存在注意定势转移能力缺陷。     

NO供体型苯骈吡喃类化合物Ⅱ-7对自发性高血压大鼠的降压作用及体外NO释放活性

目的:观察一氧化氮(NO)供体型苯骈吡喃类化合物Ⅱ-7对清醒自发性高血压大鼠(SHR)血压的影响及体外NO释放活性.方法:NO供体型苯骈吡喃类化合物Ⅱ-7分别一次性及重复多次(连续7 d)对SHR灌胃给药,测定其尾动脉收缩压(SAP)、舒张压(DAP)及心率(HR);采用Griess法测定Ⅱ-7体外NO释放量.结果:Ⅱ-7在6.0 mg/kg的剂量下一次性及连续7 d经口给药,均可非常显著地降低SHR的SAP和DAP(P＜0.01),一次性给药在降压的同时显著增加SHR的HR值(P＜0.05).体外NO释放试验结果显示,Ⅱ-7在体外能缓慢且稳定地释放NO,2.5～5.0 h内维持在较恒定的水平(0.265～0.284μg/mL).结论:NO供体型苯骈吡喃类化合物Ⅱ-7单次及重复灌胃7 d均能明显降低SHR的血压,降压作用具有一定的剂量相关性,其在体外能缓慢稳定地释放NO.     

Valsartan与benazepril联合应用对自发性高血压大鼠血压和左心室肥厚的影响

目的:评价血管紧张素转换酶抑制剂苯那普利钠和AT_1受体拮抗剂缬沙坦联合应用对自发性高血压大鼠(SHR)的降压疗效及其逆转心肌肥厚作用和对肾素-血管紧张素-醛固酮系统(RAAS)、内洋地黄素水平的影响.方法:24只14周龄雄性SHR随机分成空白对照组、Benazepril组、Valsartan组和Benazepril Valsartan组,另设WKY正常对照组.分别于药物干预前、药物干预后2、4、6、8周末测定大鼠SBP;于药物干预后8周末检测心肌组织和血浆肾素活性、血管紧张素Ⅱ浓度、心肌组织Na~ -K~ -ATP酶活性和内洋地黄素水平,并行心肌组织形态学检查.结果:药物干预各组SHR动脉收缩压(SBP)水平明显下降,尤以联合用药组SBP下降最显著;药物干预各组血浆和心肌组织肾素活性均明显升高;Benazepril组和Benazepril Valsartan组血浆和心肌组织Ang Ⅱ水平降低,而Valsartan组血浆和心肌组织Ang Ⅱ水平则明显升高;随SBP水平的降低,心肌组织Na~ -K~ -ATP酶活性明显升高,而内洋地黄素水平则明显下降;药物干预各组LVM/BW、TDM均明显减低,尤以联合用药组改变最为显著.结论:ACEI Benazepril和AT_1拮抗剂Valsartan均有明显的降低SHR的SBP作用,能明显逆转左室肥厚;联合用药效果最为显著,并能有效防止单一AT_1拮抗剂所致血浆和心肌组织Ang Ⅱ水平的升高的副作