—We investigated the role of angiotensin II (Ang II) and endothelin-1 (ET-1) in transgenic (mREN2)27 rats, a model of the monogenic renin-dependent form of severe hypertension and cardiovascular disease. Four-week-old heterozygous male transgenic (mREN2)27 rats (n=24) were matched according to body weight (BW) and blood pressure (BP) and randomly allocated to receive a placebo (group P), the mixed endothelin type A and B receptor antagonist bosentan (100 mg/kg BW PO, group B), the Ang II type 1–specific receptor antagonist irbesartan (50 mg/kg BW PO, group I), or the endothelin type A–selective antagonist BMS-182874 (52 mg/kg BW PO, group BMS). After 4 weeks of treatment, during which BW and BP were measured weekly, animals were euthanized, and the heart, left ventricle, right ventricle, adrenal gland, brain, and kidney were weighed. The plasma levels of adrenocortical steroids were measured by high-performance liquid chromatography. The tension responses of ET-free segments of the thoracic aorta to 5×10⁻⁶mmol/L phenylephrine, 60 mmol/L KCl, and cumulative doses of ET-1 were assessed. The density of ET-1 receptor subtypes in the aorta and vascular structural changes in the mesenteric arterioles (100 to 200 μm ID) were also measured with autoradiography and myography, respectively. Compared with all other groups, group I rats showed significantly (P<0.001) lower systolic BP (group I, 161±8 mm Hg; group P, 269±23 mm Hg; group B, 275±17 mm Hg; and group BMS, 254±21 mm Hg), left ventricular weight (2.28±0.15 versus 3.71±0.26, 3.38±0.27, and 3.96±0.51 mg/g BW, respectively), tension responses to vasoconstrictors, and normalized media thickness of the mesenteric arterioles (22.3±0.6 versus 25.3±0.5, 25.5±0.7, and 24.1±1.5 μm, respectively). Compared with levels in group P (78±25 pmol/mL), plasma aldosterone levels were significantly decreased in group B (51±11 pmol/mL) and group I (40±16 pmol/mL). Thus, endogenous ET-1 and Ang II contribute to the regulation of aldosterone, but only Ang II is crucial for the development of hypertension and related target organ damage via the Ang II type 1 receptor. Endogenous Ang II does not appear to enhance cardiovascular production of ET-1 in this model of hypertension within the time span of our experiment.

Methylphenidate is a piperidine derivative and is the drug most often used to treat attention deficit/hyperactivity disorder of children and young adults. Our aim is to investigate dose-dependent dopamine-2 receptor and glial fibrillary acidic protein expression and ultrastructural changes of the rat brain, to demonstrate possible toxicity of the long-term and high dose use of the methylphenidate. In this study, 27 female prepubertal Wistar albino rats, divided into three different dose groups (5, 10 and 20 mg/kg) were treated orally with methylphenidate dissolved in saline solution for 5 days per week during 3 months. At the end of the third month, tissues were removed and sections were collected for immunohistochemical and ultrastructural studies. We believe that methylphenidate causes dose-related activation of the dopaminergic system in several brain regions especially in ventral tegmental area and also causing neuronal degeneration and capillary wall structural changes such as basal membrane thickness and augmentation of the pinostatic vesicle in the endothelial cells. Also, increased dose of Ritalin is inducing astrocytes hypertrophy especially astrogliosis in pia-glial membrane and this is the result of the degenerative changes in prefrontal cortex region due to high dose methylphenidate administration. The dose-related accumulation of the astrocytes in capillary wall might well be a consequence of the need for nutrition of the neuronal tissue, due to transport mechanism deficiency related to neuronal and vascular degeneration. Thus, we believe that the therapeutic dose of methylphenidate must be kept in minimum level to prevent ultrastructural changes.

The aim of this study was to compare the ultrastructural alterations of the muscle and nerve that appear following injection of freshly reconstituted and stored botulinum toxin A. Fifteen New Zealand white rabbits were assigned to 6 groups, and anterior auricular muscle was used for injections. Group 1 did not receive any injection and group 2 received saline injection. Groups 3 and 5 received fresh botulinum; muscles and motor nerves were harvested at 5 days and 12 weeks, respectively. Groups 4 and 6 received stored botulinum; muscles and motor nerves were harvested at 5 days and 12 weeks, respectively. Alterations in muscle and nerve ultrastructure were evaluated with electron microscopy. Degeneration findings in muscle after botulinum toxin injection revealed no significant difference between freshly reconstituted and stored toxin in the early period. When stored toxin was used, atrophic changes in the muscle were less severe than the fresh toxin at 3 months. On nerve evaluation, fresh toxin displays significant acute changes on nerve ultrastructure; however, fresh and stored toxin shows similar degeneration at 12 weeks.