Dopamine D3 receptors in the rat kidney: role in physiology and pathophysiology

It is well accepted that dopamine receptors play an important role in the regulation of cardiovascular and kidney function. Most of the knowledge on the renal actions of dopamine has been accumulated focussing on the prototypes of the two known dopamine receptor subfamilies, i.e. D₁ and D₂. The dopamine D₃ receptor is a member of the D₂‐like subfamily and has been intensively studied in the neurosciences. Recently, the peripheral actions of this receptor subtype have also raised considerable interest as well because its effects on kidney function appear to be different from that of the other dopamine receptors. This short overview will summarize the data reported and add new results on the role of D₃ receptors in the regulation of renal function as well as their potential pathophysiological implications.     

ROLE OF UTERINE FACTORS IN THE DEVELOPMENT OF HYPERTENSION IN SHR

1. To examine whether the uterine environment plays a role in the development of hypertension in the spontaneously hypertensive rats (SHR), we have compared fetal weight, placental weight, and amniotic fluid composition of SHR and Wistar-Kyoto (WKY) rats after 20 days of gestation. 2. Pregnant SHR and WKY were anaesthetized at 20 days of gestation and the uterus and embryonic sacs removed. Fetal and placental weights were recorded and amniotic fluid collected for measurement of volume, osmolality and electrolyte composition. 3. No significant difference was found in litter size and placental weight between SHR and WKY. Total embryonic sac weight and fetal weight of SHR were significantly lower than WKY. Amniotic fluid volume, sodium concentration and osmolality of SHR were significantly higher than WKY, while amniotic fluid potassium concentration of SHR was significantly lower than WKY. 4. Thus, the SHR foetus was significantly underweight compared to the WKY and was bathed in amniotic fluid with a significantly higher osmolality and sodium concentration. As the mature foetus is known to drink amniotic fluid, it is hypothesized that the elevated Na/K ratio in SHR amniotic fluid may instigate or accelerate the hypertensive process.     

降压药物对未成年自发性高血压大鼠血管平滑肌细胞增生与凋亡及相关基因蛋白的影响

目的　观察不同种类降压药物对未成年自发性高血压大鼠 (SHR)主动脉血管平滑肌细胞 (VSMC)增生和凋亡的影响 ,探讨其在高血压早期血管重塑中的作用和意义。方法　 36只 4周龄SHR ,按随机化区组设计分成6组 ,分别应用普萘洛尔 ( 5 0mg·kg-1·d-1)、依那普利 ( 30mg·kg-1·d-1)、硝苯地平 ( 35mg·kg-1·d-1)、缬沙坦 ( 30mg·kg-1·d-1)、双氢氯噻嗪 ( 75mg·kg-1·d-1)干预 6周。另设一对照组 ,采用末端脱氧核苷酸转移酶 (TdT)介导的dUTP缺口末端标记法 (TUNEL)检测凋亡细胞 ;用免疫组化法检测Bcl 2、Bax基因蛋白 ;光镜下观察主动脉组织学改变。结果　 ( 1)依那普利、硝苯地平和缬沙坦组VSMC凋亡指数 (SMCAI)显著增高 (P <0 .0 1) ,而普萘洛尔、双氢氯噻嗪组与对照组相比较无显著性差异 (P >0 .0 5 )。 ( 2 )依那普利和缬沙坦组Bcl 2基因表达较对照组显著下降 (P <0 .0 1) ,硝苯地平组也显著下降 (P <0 .0 5 ) ,而普萘洛尔、双氢氯噻嗪组与对照组比较无显著性差异 (P>0 .0 5 )。 ( 3)缬沙坦组Bax基因表达较对照组显著增高 (P <0 .0 1) ,余 4组与对照组比较无显著性差异 (P >0 .0 5 )。 ( 4 )依那普利、硝苯地平和缬沙坦组Bcl 2 /Bax较对照组显著下降 (P <0 .0 1) ,而普萘洛尔、双氢氯噻组与对照组比较     

Developmental programing of thirst and sodium appetite

Thirst and sodium appetite are the sensations responsible for the motivated behaviors of water and salt intake, respectively, and both are essential responses for the maintenance of hydromineral homeostasis in animals. These sensations and their related behaviors develop very early in the postnatal period in animals. Many studies have demonstrated several pre- and postnatal stimuli that are responsible for the developmental programing of thirst and sodium appetite and, consequently, the pattern of water and salt intake in adulthood in need-free or need-induced conditions. The literature systematically reports the involvement of dietary changes, hydromineral and cardiovascular challenges, renin–angiotensin system and steroid hormone disturbances, and lifestyle in these developmental factors. Therefore, this review will address how pre- and postnatal challenges can program lifelong thirst and sodium appetite in animals and humans, as well as which neuroendocrine substrates are involved. In addition, the possible epigenetic molecular mechanisms responsible for the developmental programing of drinking behavior, the clinical implications of hydromineral disturbances during pre- and postnatal periods, and the developmental origins of adult hydromineral behavior will be discussed.     

化痰祛浊通络方对自发性高血压大鼠血压一氧化氮、内皮素1及血管紧张素Ⅱ的影响

目的：观察化痰祛浊通络方对自发性高血压大鼠（SHR）血压及一氧化氮（NO）、内皮素1（ET－1）及血管紧张素Ⅱ（AngⅡ）的影响,探讨其降压作用机制。方法将15月龄SHR随机分为空白对照组、化痰祛浊通络方组和吲达帕胺组,每组各9只。空白对照组予0．9％氯化钠注射液（10 mL／kg）、化痰祛浊通络方组予化痰祛浊通络方水煎液（生药10 mL／kg）、吲达帕胺组予吲达帕胺溶液（10 mg／kg）,均每日1次灌服,连续6周。所有大鼠每周测量尾动脉压,给药6周腹主动脉抽血测定血清NO、ET－1及AngⅡ含量。结果给药6周后,化痰祛浊通络方组和吲达帕胺组给药后均可降低SHR收缩压（ SP）和舒张压（ DP）,与空白对照组及本组给药前比较差异均有统计学意义（P＜0．05）;化痰祛浊通络方组及吲达帕胺组ET－1和AngⅡ含量均较本组给药前及空白对照组明显降低,NO含量明显升高,差异均有统计学意义（P＜0．05）。结论化痰祛浊通络方能明显降低SHR血压,其机制可能是通过下调ET、Ang Ⅱ含量及上调NO含量来发挥降压作用。     

通心络治疗对自发性高血压大鼠心肌纤维化的影响

目的：观察通心络对自发性高血压大鼠(SHR)心肌纤维化的影响。方法：30只12周龄雄性SHR大鼠，随机分成大剂量通心络组、小剂量通心络组、SHR空白对照组3组，每组10只；另取10只同龄雄性正常血压WKY大鼠作为对照组。给药12周，天狼星红染色法使肢原特殊染色，计算机图像分析测量心肌切片的肢原容积分数和心肌小动脉周围肢原面积与小动脉面积比表示心肌纤维化程度；放免法(RIA)测定血浆AngⅡ的浓度：结果：与SHR组相比，大、小剂量通心络组均能在一定程度上抑制S服血压升高(P＜0．05)。通心络大、小剂量组治疗均能在一定程度上改善SHR大鼠左心室肥厚(P＜0．05)，并使心室内、外膜及心肌小动脉周围的胶原减少，同时血浆AngⅡ浓度较SHR组下降，其中大剂量组各指标均较SHR有统计学意义(P＜0．05)。结论：通心络对SHR大鼠的心肌纤维化有显著的抑制作用。     

短期氟伐他汀治疗对自发性高血压大鼠阻力血管肥厚的影响

目的探讨氟伐他汀（一种ＨＭＧ－ＣｏＡ还原酶抑制剂）对自发性高血压大鼠阻力血管结构和血压进程的影响。方法１４只８周龄雄性ＳＨＲ大鼠，氟伐他汀２０ｍｇｋｇ－１ｄ－１灌胃，作为治疗组（ＳＨＲｆｌｕ），同周龄、同性别给于安慰剂的ＳＨＲ和ＷＫＹ大鼠作对照组。用计算机图象分析计算血管壁腔比，以观察三组大鼠肠系膜动脉三级分支及主动脉结构变化。结果８周后，氟伐他汀治疗组（ＳＨＲｆｌｕ）收缩压比对照组（ＳＨＲ）平均下降了２１ｍｍＨｇ（１９１±１３ｍｍＨｇｖｓ２１２±８ｍｍＨｇ，Ｐ＜０．０５）。ＳＨＲｆｌｕ肠系膜动脉三级分支比ＳＨＲ的血管壁薄，管腔大，血管的壁腔比显著小于未治疗的ＳＨＲ（Ｐ＜０．０５）。结论短期氟伐他汀治疗，抑制了ＳＨＲ大鼠血压发展过程中伴随的血管壁肥厚现象，延缓了ＳＨＲ大鼠高血压的进程。     

唇香草挥发油对自发性高血压大鼠降压作用的研究

目的：探讨唇香草挥发油对自发性高血压大鼠（SHR）的降压作用。方法采用随机数字表法将60只 SHR 大鼠随机分为6组,模型对照组（生理盐水）、卡托普利组（20 mg/kg）、氢氯噻嗪组（20 mg/kg）、唇香草挥发油高（40 mg/kg）、中（20 mg/kg）、低（10 mg/kg）剂量组,另外10只 Wista 大鼠作为空白对照,分别进行药物干预4周,于给药前后2h 测定各组大鼠尾动脉血压。结果给药3 w 后唇香草挥发油高、中剂量组及卡托普利、氢氯噻嗪组 SHR 大鼠收缩压、舒张压均显著低于阳性对照组（P ＜0．05）。结论唇香草挥发油对 SHR 大鼠具有显著的降压作用。     

Effect of Prepuberal Gonadectomy upon Aldosterone Levels in Female and Male SHR: Interaction between Blood Pressure and Kallikrein Kinin System

It has been suggested that an abnormal activity of the hypothalamic-pituitary-adrenal-gonadal axis may be implicated in the pathogenesis of spontaneously hypertensive rats (SHR) blood pressure hypertension. However, it is widely known that the kallikrein-kinin system plays a role in blood pressure regulation in this strain, because an inverse relation between blood pressure and urinary kallikrein excretion has been reported. It was of our interest to study how early suppression of sexual hormones affected blood pressure regulation in SHR and urinary kallikrein excretion and to elucidate the involved mechanisms. For these purpose, SH and Wistar-Kyoto (WKY) rats blood pressure, renal function, and hormonal profile were studied after prepuberal gonadectomy starting at 4 weeks of age throughout until the 12th week of age. Results were compared with those of untreated SH and WKY rats of either sex. The response to blocking agents against aldosterone and kallikrein-kinin system also were evaluated. Systolic blood pressure increased progressively in male and female SHR 12 weeks of age. Systolic blood pressure was higher in male than in female SHR, but urinary kallikrein was lower in male SHR. Prepuberal gonadectomy induced a significant decrease in systolic blood pressure in male and in female SHR at 12 weeks of age, accompanied by an increase in urinary kallikrein in male and in female SHR. Plasma aldosterone increased markedly in female and male SHR after gonadectomy. No concurrent changes in plasma renin activity or corticosterone levels were observed. The aldosterone receptor antagonist and the kallikrein inhibitor treatment blunted the blood pressure lowering effect of gonadectomy and diminished urinary kallikrein excretion. Results support the existence of a sexual dimorphism related to hypertension and urinary kallikrein and suggest an interaction among the kallikrein-kinin system, sexual hormones, and mineralocorticoids in the neonatal programming of hypertension.