Apocynin activity in spontaneously hypertensive rats (SHR): preliminary studies in vivo

An elevation in angiotensin II (Ang II) levels is a common occurrence in spontaneously hypertensive rats (SHRs). Infusions of Ang II and a high salt diet increase the activity of NADPH oxidase that stimulates superoxide anion (O⁻²) generation and increases the expression of certain subunits of NADPH oxidase. Apocynin, an NADPH oxidase inhibitor with antihypertensive effects, is able to inhibit the release of superoxide anion by inhibiting NADPH oxidase activity and blocking the migration of p47 phox to the mitochondrial membrane. The aim of our study was to evaluate the antihypertensive effects of apocynin in SHRs and Wistar rats (WKYs) using a micropuncture technique. After microperfusion of both the proximal and distal tubules, we found that SHRs treated with apocynin showed a decrease in the free-flow collection of the proximal tubule (PT), which was not affected in WKYs. Moreover, significant differences were not demonstrated in the distal tubule (DT), probably due a mechanism of compensation that occurs in the loop of Henle. In conclusion, it is possible that the mechanisms of reabsorption in the PT are controlled by the interactions of O⁻² and nitric oxide (NO). These data could suggest a higher activity of NADPH oxidase and increase in reactive oxygen species (ROS) production in the PT during hypertension.

     

Immunohistochemical findings of juxtaglomerular cells on acute phase in two-kidney Goldblatt hypertensive rats and spontaneously hypertensive rats.

Juxtaglomerular (JG) cells on the acute phase in two-kidney Goldblatt hypertensive (2KGH) rats and spontaneously hypertensive rats (SHR) were examined immunohistochemically. JG cells in 2KGH rats and SHR were positively stained with anti-renin serum and anti-angiotensin II (A II) serum. In 2KGH rats, the number of renin and AII immunoreactive JG cells in the clipped kidneys increased throughout the observation period. The number of renin and AII immunoreactive JG cells in the unclipped kidneys was almost the same as that in control rats, although immunoreactivity of these cells was weak and they were small in size. These changes in the unclipped kidneys became obvious with the time course after operation. We did not see any changes in these cells in SHR. In 2KGH rats treated with captopril, the number of renin immunoreactive JG cells in the clipped kidneys increased, whereas that of AII immunoreactive JG cells in the bilateral kidney decreased. When captopril was administered to SHR, the number of renin immunoreactive JG cells in the bilateral kidney increased, whereas that of AII immunoreactive JG cells in the bilateral kidney decreased. These results suggested that the JG cell in the bilateral kidney was closely related to the development of hypertension in 2KGH rats, but not in SHR. The increase of renin immunoreactive JG cells in 2KGH rats and SHR treated with captopril was probably due to the removal of negative feedback inhibition of AII on JG cells.     

Doublecortin-immunoreactive neuronal precursors in the dentate gyrus of spontaneously hypertensive rats at various age stages: comparison with Sprague-Dawley rats

Spontaneously hypertensive rats (SHRs) are widely accepted in medical research because this model has been used for studies in neurodegenerative diseases such as vascular dementia and stroke. In the present study, we observed newly generated neuronal precursors using doublecortin (DCX, a marker of neural proliferation and differentiation) in the subgranular zone of the dentate gyrus in SHRs compared to Sprague-Dawley rats (SDRs) at various age stages. DCX immunoreactivity, immunoreactive cell numbers and its protein level in the dentate gyrus of the SHRs were higher than those in the SDRs at postnatal month 1 (PM 1). At PM 8, DCX immunoreactivity, immunoreactive cell numbers and protein levels in both groups were markedly decreased compared to those at PM 1; however, they were higher than those in the SDRs. They were decreased in the both groups with age: DCX immunoreactive cells in the SDRs were few at PM 12. Our results indicate that newly generated neuronal precursors are more abundant in SHRs than in SDRs during their life.     

NaCl plus chitosan as a dietary salt to prevent the development of hypertension in spontaneously hypertensive rats

The effect of NaCl plus 3% chitosan on the systolic blood pressure of spontaneously hypertensive rats (SHR) were evaluated and compared with NaCl plus KCl (NaCl, 49.36% + KCl 49.36%) and chitosan or NaCl treatment alone. In SHR, administration of NaCl plus chitosan (44 mM Na/day) for two months significantly decreased the systolic blood pressure greater than of NaCl plus KCl and NaCl alone. NaCl plus chitosan resulted, though not statistically significant, in decreased urinary Na⁺ excretion and decreased blood urea nitrogen levels. Urinary creatinine of NaCl plus chitosan was slightly decreased compared to 3 treated groups. Serum electrolytes levels, however, remained unchanged. The combination of NaCl and chitosan may be superior to the conventional use of NaCl plus KCl or NaCl alone in the prevention of hypertension. Even though these supplementary diets have demonstrated potential anti-hypertensive effects in the experimental animal model, further research is needed before any recommendations can be made.     

Assessment of halothane and sevoflurane anesthesia in spontaneously breathing rats

OBJECTIVE: To characterize halothane and sevoflurane anesthesia in spontaneously breathing rats. ANIMALS: 16 healthy male Sprague-Dawley rats. PROCEDURE: 8 rats were anesthetized with halothane and 8 with sevoflurane. Minimum alveolar concentration (MAC) was determined. Variables were recorded at anesthetic concentrations of 0.8, 1.0, 1.25, and 1.5 times the MAC of halothane and 1.0, 1.25, 1.5, and 1.75 times the MAC of sevoflurane. RESULTS: Mean (+/- SEM) MAC for halothane was 1.02 +/- 0.02% and for sevoflurane was 2.99 +/- 0.19%. As sevoflurane dose increased from 1.0 to 1.75 MAC, mean arterial pressure (MAP) decreased from 103.1 +/- 5.3 to 67.9 +/- 4.6 mm Hg, and PaCO2 increased from 58.8 +/- 3.1 to 92.2 +/- 9.2 mm Hg. As halothane dose increased from 0.8 to 1.5 MAC, MAP decreased from 99 +/- 6.2 to 69.8 +/- 4.5 mm Hg, and PaCO2 increased from 59.1 +/- 2.1 to 75.9 +/- 5.2 mm Hg. Respiratory rate decreased in a dose-dependent fashion from 88.5 +/- 4.5 to 58.5 +/- 2.7 breaths/min during halothane anesthesia and from 42.3 +/- 1.8 to 30.5 +/- 4.5 breaths/min during sevoflurane anesthesia. Both groups of rats had an increase in eyelid and pupillary aperture with an increase in anesthetic dose. CONCLUSIONS AND CLINICAL RELEVANCE: An increase in PaCO2 and a decrease in MAP are clinical indicators of an increasing halothane and sevoflurane dose in unstimulated spontaneously breathing rats. Increases in eyelid aperture and pupil diameter are reliable signs of increasing depth of halothane and sevoflurane anesthesia. Decreasing respiratory rate is a clinical indicator of an increasing dose of halothane.     

Distinct and combined effects of acute immobilization and chronic isolation stress on MAO activity and antioxidative protection in the heart of normotensive and spontaneously hypertensive rats

The heart is an organ especially sensitive to the sympathetic overstimulation and therefore to the influence of stressors and hypertension. The aim of the present study was to investigate the effect of two distinct types of stressors, acute immobilization (2 h) and chronic isolation stress (21 days), as well as their combined effect on the activity of monoamine oxidase (MAO), superoxide dismutase, catalase (CAT) and the ascorbic acid (AA) content in the heart of normotensive and spontaneously hypertensive rats (SHR). The results obtained show that in basal conditions heart MAO and CAT activity (p < 0.05), as well as AA concentration (p < 0.01) were higher in SHR than in normotensive ones. The acute immobilization significantly decreased heart MAO activity in both examined strains (p < 0.01). On the other hand, chronic isolation, separately or in combination with immobilization, did not affect this enzyme, in the heart of either hypertensive or normotensive rats, which was associated with the reduced antioxidative protection (p < 0.01, p < 0.05).     

Blood pressure characteristics of female spontaneously diabetic Torii-Lepr(fa) rats

Blood pressure in female SDT-fa/fa rats was periodically investigated at ages 8, 16, and 24 weeks. Furthermore, an insulin therapy was performed for 5 weeks in the female rats at age 11 weeks, and the change of blood pressure was examined. In addition to obesity, hyperglycemia, hyperinsulinemia, and hyperlipidemia, hyperleptinemia and increased urinary angiotensinogen level were observed during the experimental period. Blood pressure was elevated at ages 8 and 16 weeks, but that at 24 weeks was comparable to that in Sprague-Dawley (SD) rats. Heart rate was decreased from age 8 to 24 weeks. Insulin therapy induced good glycemic control and improvement of hyperlipidemia, but the blood pressure was not reduced. Blood pressure in female SDT-fa/fa rats was elevated temporarily. The blood pressure was not decreased by insulin treatment. SDT-fa/fa rat is a useful model to investigate the relation between diabetes mellitus and hypertension.     

济生肾气丸治疗大鼠实验性肾炎的试验研究

观察济生肾气丸对大鼠实验性肾炎的药理作用。结果表明 ,阿霉素肾炎及小牛血清白蛋白性肾炎均能引起大鼠尿蛋白排出增加 ,血清尿素氮及血清肌酐含量升高 ,而给药组动物上述指标明显改善。表明本方对大鼠实验性肾炎有明显的治疗作用。     

The granular layer of Tomes in experimental caries in rats

In examination of ground sections of human third maxillary molar teeth, the granular layer of Tomes was shown to consist of expansion of dentinal tubules. The microradiographic density was decreased well inside the layer. It was postulated that the findings were expressions of dentin resorption. The theory was tested experimentally in rats fed a cariogenic diet with low calcium and phosphorus. The morphology of mandibular molar teeth was studied by electron probe microanalysis and by microradiography. It was concluded that the primary event in cariogenesis was an expansion of peripheral dentinal tubules with formation of confluent microcavities and, thus, an unmasking of the granular layer of Tomes, which normally is only potential. A subsequent loss of mineral density in the outer enamel eventually caused breakdown of the outer enamel with caries visible from the surface. The loss of density within the enamel was postulated to result from interruption of the normal flux of nutrients, metabolites and ions between the dentin and enamel. Whereas an increase in dietary calcium and phosphorus delayed and reduced significantly, but did not prevent cariogenesis, it supported the theory that experimental caries in rats is a metabolic disease with the peripheral dentin the primary target.