ABSTRACT
To evaluate the effects of angiotensin converting enzyme inhibitor (ACE-I) on diabetic cardiovascular complications, a streptozotozin (STZ, i.p., 70 mg/kg BW) induced diabetes rat model was used. The animals were separated into four major groups including: control (NSS), STZ-treated rats, STZ-treated rats received daily oral feeding of cilazapril starting one day after STZ injection (STZ-C1), and STZ-treated rats received daily oral feeding of cilazapril eight weeks after the STZ injection (STZ-C8). Within the groups of STZ-C1 and STZ-C8, the animals were also divided into three subgroups of six rats that received different doses of cilazapril treatment, 0.01 mg/Kg BW, 1 mg/Kg BW, and 10 mg/Kg BW. By using the modified isolated heart model, the parameters of mean arterial pressure (MAP), heart rate (HR), left ventricular isotonic contraction (LVIC), aortic flow rate (AFR), coronary flow rate (CFR), and ratio of heart weight per body weight (R) were assessed for each groups 8 and 20 weeks after the STZ injections. Moreover, the changes of wall thickness of the left ventricular wall (LV), right ventricular wall (RV), and interventricular septal wall (IVS) were monitored from the scanning electron micrographs of each heart. The results indicated that in both STZ-C1 and STZ-C8, the diabetic hypertension could be prevented or treated by anti-hypertensive doses of cilazaprils. Besides, the values of AFR, CFR, and LVIC were significantly increased when comparing between the STZ and STZ-C1 or STZ-C8. The results of morphological examinations indicated that: (1) left ventricular walls of the three hearts of STZ-rats had increased significantly more than controls. (2) Right ventricular walls and interventricular septal walls were not significantly different among STZ-rats, cilazapril treated STZ-rats and age matched controls. Therefore, it is concluded that ACE-I could act either as a cardioprotective or therapeutic agent for diabetic hearts. Both major anti-hypertension and anti-trophic effects of ACE-I have already been elucidated.
Subject(s)
Administration, Oral , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Cardiovascular Diseases/drug therapy , Cilazapril/pharmacology , Diabetes Mellitus, Experimental/chemically induced , Diabetic Angiopathies/drug therapy , Disease Models, Animal , Dose-Response Relationship, Drug , Hypertension/prevention & control , Male , Probability , Rats , Rats, Wistar , Reference Values , Sensitivity and Specificity , StreptozocinABSTRACT
Hipertensão arterial sistêmica ocorre em 40 por cento a 90 por cento dos pacientes com síndrome de apnéia do sono tipo obstrutivo (SASO). A SASO, por sua vez, é encontrada em um terço dos pacientes previamente diagnosticados como tendo hipertensão essencial. O tratamento da SASO nestes casos leva à melhora da hipertensão. A fisiopatologia subjacente ao desenvolvimento de hipertensão pela SASO, inicialmente durante o sono e gradualmente acometendo o período de vigília envolve os altos níveis de atividade nervosa simpática deflagrados pelas apnéias. Há prolongamento progressivo dos níveis elevados, particularmente de noradrenalina, durante o período de vigília
Subject(s)
Humans , Male , Hypertension , Sleep Apnea Syndromes/complications , Antihypertensive Agents , Cilazapril/pharmacology , Sleep Apnea Syndromes/therapyABSTRACT
El aumento mantenido de las resistências vasculares periféricas es la alteración hemodinámica que caracteriza a la hipertensión arterial (HTA) establecida. Ello es el resultado de un incremento del tono vascular y los cambios estructurales que implican tanto la hipertrofia e hiperplasia de las fibras musculares lisas vasculares, la hipertrofia de las células cardíacas y un aumento de la síntesis de los componentes de la matriz extracelular. La angiotensina ll y la noradrenalina ejercen importantes efectos tróficos que aceleran la progresión de la hipertrofia cardiovascular siendo el aparato cardiovascular muy sensible a las acciones tróficas del sistema renina-angiotensina. La angiotensina ll induce la expresión de la cadena A del factor de crecimiento de origen plaquetario, del factor de crecimiento fibroblástico básico y del factor transformador B y además estimula la síntesis de colágeno tipo I y II y facilita la liberación de factores tróficos. Por lo tanto, el sistema renina-angiotensina juega un importante papel en la regulación del crecimiento y remodelación de los miocitos y de la matriz extracelular cardiovascular, que está mediado a través de receptores específicos, ya que puede inhibirse por antagonismo de los receptores ATl para la angiotensina II e IECA. El cilazapril es un IECA de larga duración que produce una reducción de la presión arterial y de la hipertrofia cardiovascular. El mecanismo responsable de esta acción es múltiple como su acción vasodilatadora, su capacidad para inhibir el tono simpático o para aumentar los niveles de kininas y particularmente su capacidad de inhibir el sistema renina-angiotensina cardíaco.