RESUMO
Statins can increase endothelial function through enhancement of the expression and activity of endothelial nitric oxide synthase (eNOS). The aim of this study is to evaluate the effect of rosuvastatin on the number of circulating endothelial progenitor cells (EPCs) and endothelial expression of eNOS in monocrotaline-induced pulmonary hypertensive rats. Sixty Sprague-Dawley (SD) rats were divided into three groups of 20: control (group A), pulmonary hypertension (PAH) + rosuvastatin group (group B), and PAH (group C). Monocrotaline (MCT; 60 mg/kg) was injected (intraperitoneally) to induce PAH. Rats in group B received rosuvastatin [10 mg/(kg. day)] for 2 weeks. Peripheral blood (5 mL) was aspirated from the femoral artery of each rat before and after 2 weeks of treatment. Mononuclear cells were isolated and subcultured to obtain EPCs. Small and moderately sized pulmonary arteries were collected 2 weeks later for histological analyses. eNOS gene expression in endothelial cells of pulmonary arteries were then determined at mRNA and protein levels. eNOS expression at mRNA and protein levels and the number of circulating EPCs were reduced significantly in groups B and C compared with group A (P less than 0.05), and a significant difference between group B and group C (P less than 0.05) was observed. Vascular remodeling in small and moderately sized pulmonary arteries was attenuated markedly in group B compared with group C. These results suggest that rosuvastatin can ameliorate the remodeling of pulmonary arteries in MCT-induced PAH rats by increasing the number of circulating EPCs and eNOS upregulation.
Assuntos
Células Progenitoras Endoteliais/efeitos dos fármacos , Hipertensão Pulmonar/tratamento farmacológico , Óxido Nítrico Sintase Tipo III/biossíntese , Rosuvastatina Cálcica/uso terapêutico , Remodelação Vascular/efeitos dos fármacos , Animais , Arteríolas/patologia , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos , Células Progenitoras Endoteliais/enzimologia , Endotélio Vascular/fisiopatologia , Indução Enzimática/efeitos dos fármacos , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/fisiopatologia , Masculino , Monocrotalina/toxicidade , Óxido Nítrico Sintase Tipo III/genética , Artéria Pulmonar/patologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Túnica Média/ultraestrutura , Regulação para Cima/efeitos dos fármacosRESUMO
San Zhuang Wan (SZW) is a traditional Chinese herbal medicine used to treat male impotence. The mechanism of its therapeutic effect is not known nor have any of its potential physiologic actions been investigated. We examined the effect of SZW administered by gavage, on the reproductive system of the prepubertal male rat. After 10 days treatment of 21-day-old rats the concentration of testosterone in serum and testicular weight had decreased whereas the serum concentration of luteinizing hormone (LH) had significantly increased. When administered to gonadectomized rats SZW partially restored the weight of the accessory sex organs and concentration of LH toward normal, but serum androgen concentration was not changed. In vitro assessment of fragments of testicular tissue or purified Leydig cells for responsiveness to maximal doses of LH or cyclic AMP showed that SZW significantly reduced testosterone secretion in response to either stimulant. The data demonstrate that SZW has potent effects on the reproductive axis of the pubertal male rat. At least one locus for such action is on the Leydig cell at a point distal to the formation of cyclic AMP. Further study is necessary to determine whether these effects could be involved with or independent of the mechanism of the therapeutic action of SZW.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Castração , Hormônio Luteinizante/sangue , Masculino , Tamanho do Órgão , Ratos , Ratos Endogâmicos , Testículo/anatomia & histologia , Testosterona/sangueRESUMO
In this study, the effect of the herbal prescription Tian Ma Gou Teng Yen (TGY), which is traditionally used to treat certain diseases associated with elevated arterial pressure (AP), on the general development of hypertension was investigated in the spontaneously hypertensive rat (SHR). An aqueous extract of TGY was given orally (0.5 ml/100g body weight) to 5 week old SHR twice a day for six consecutive days followed by one day without herbal therapy. The herbal prescription was administered until the SHR were 16 weeks of age. Administration of TGY significantly altered the development and prevented hypertension in SHR. On the other hand, heart rate, body weight, food and water intake, and urine volume and electrolytes were not altered. These data suggest that the effect of TGY on AP was through an action of TGY on sympathetic vasomotor activity.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Hipertensão/prevenção & controle , Animais , Medicamentos de Ervas Chinesas/uso terapêutico , Rim/efeitos dos fármacos , Masculino , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Endogâmicos SHR , Urodinâmica/efeitos dos fármacosRESUMO
Two series of experiments were done in male Wistar rats to investigate the effects of lesions of the paraventricular nucleus of the hypothalamus (PVH) on the maintenance and development of the elevated arterial pressure resulting from denervation of aortic baroreceptors. In the first series, after control recordings of arterial pressure (AP) and heart rate (HR), rats were subjected to either bilateral aortic depressor nerve (ADN) transection or sham-ADN transection. These animals were later subjected to either bilateral lesions of the PVH or sham-PVH lesions. AP (146 +/- 2 mm Hg) and HR (515 +/- 5 bpm) were significantly elevated in only the ADN-transected groups. Bilateral lesions of the PVH significantly reduced AP (119 +/- 3 mm Hg) and HR (440 +/- 8 bpm) in the ADN transected animals compared to ADN-transected sham-PVH-lesioned animals, to levels which were not significantly different from pre-ADN-transected levels (AP, 113 +/- 2 mm Hg; HR, 448 +/- 3 bpm), and from sham-ADN-transected PVH-lesioned (AP, 119 +/- 2 mm Hg; HR, 391 +/- 6 bpm) and sham-ADN-transected sham-PVH-lesioned animals (AP, 116 +/- 2 mm Hg; HR, 436 +/- 4 bpm). In the second series of experiments, after control AP and HR recordings rats were first subjected to either bilateral lesions of the PVH or sham-PVH lesions, and second to either bilateral ADN transection or sham-ADN transection. PVH lesions did not significantly alter the AP and HR from control levels.(ABSTRACT TRUNCATED AT 250 WORDS)