Simvastatin improves vascular reactivity of rabbit aorta irrespective of its hypocholesterolemic effect

Simvastatin is one of the 3-Hydroxy-3-methylglutaryl coenzyme A reductase [HMG-Co-A] inhibitors known for their hypocholesterolemic effect. Apart from cholesterol lowering, simvastatin exerts other beneficial effects such as reduction of plasma fibrinogen and platelet aggregation, anti-inflammatory, anti-proliferative effects, and decreasing risk of coronary heart disease [CHD] and myocardial infarction. This work aimed at investigating the possible modifying effect of simvastatin on systemic vascular reactivity. Vascular responses to various vasoactive agents were tested on isolated rabbit aortic ring preparations obtained at the end of 16 week duration from control normocholesterolemic [group 1], hypercholesterolemic [group 2] as well as simivastatin-treated normocholesterolemic [group 3] and simvastatin-treated hypercholesterolemic [group 4] animal groups. Hypercholesterolemia was induced in groups 2 and 4 by a high cholesterol diet for the 16 weeks. Treated groups [3 and 4] received simvastatin in a daily dose of 10 mg/kg for 8 weeks starting by the beginning of the 9[th] week. In addition to vascular reactivity studies, plasma cholesterol levels were measured for all animals at the ends of 4[th], 8[th], 12[th] and 16[th] weeks. Simvastatin pretreatment significantly reduced plasma cholesterol levels in group 4 animals in comparison to group 2, decreased contractile responses to nor epinephrine [NE] and augmented relaxation induced by acehylcholine [ACh] in nomocholesterolemic [group 3] and treated hypercholesterolemic [group 4] animals compared with control or hypercholesterolemic groups, respectively. In addition, it augmented sodium nitroprusside [SNP] induced relaxant responses in tissues obtained from group 4 compared with group 2. The vasoprotective effects observed with simivastatin therapy may be mainly attributed to improvement of vascular endothelial function not only under hypercholesterolemic- but also normocholesterolemic conditions. Thus simvastatin therapy may be applied not only to reduce the risk of CHD but also the systemic vascular complications associated with hypercholesterolemia. In addition simvastatin might serve as a prophylactic agent against disturbed vascular reactivity that may develop under certain pathological conditions devoid of hypercholesterolemia

Comparison between the effect of bosentan and perindopril on diabetic angiopathy and nephropathy in streptozotocin-induced diabetic rats

Angiopathy and nephropathy are serious problems encountered in the management of diabetes, mellitus. There is accumulating literatrues describing some sort of hystological interaction between angiotensin II [ALI] and endothelins [ETs] in addition to their possible contributing roles in the pathogenesis of diabetic complications. In the present study, the angiotensin converting enzyme inhibitor [ACEI] perindopril to prevent or minimize the development of angiopathy [endothelial dysfunction] and nephropathy in a strepozotocininduced model of diabetes type I in albino rats. Animals were classified into six groups: untreated healthy non diabetic [ND] control rats, healthy [ND] rats treated with perindopril [3 mg/kg/day], healthy [ND] rats treated with bosentan [100 mg/kg/day], untreated diabetic rats, and diabetic rats treated with either perindopril or bosentan in the same doses described before. Rats were rendered diabetic by a single injection, in the tail vein, of 55 mg/kg streptozotocin [STZ] after overnight fast. Treatment with bosentan and perindopril was continued for 16 weeks during which the 24[th] urine volume, urinary albumin content, urine and plasma levels of creatinine as well as systolic blood pressure [SBP] were assessed at the end of each 4 weeks. At the end of the 16[th] week rats were sacrificed and the kidneys were removed for examination of histopathological changes, while the thoracic aortae were removed for assessment of the vasorelaxant effect of acetylcholine [Ach]. Diabetic rats developed typical functional changes manifested by hyperglycemia, polyuria, albuminuria, elevated SBP, reduced response to vasorelaxant effect of ACh in addition to histopathological changes manifested by tubular dilatation, diffuse interstitial edema and decreased density of the brush border of epithelial cells. In the healthy [ND] animals, changes obtained in the different parameters studied were insignificant between the treated and non-treated groups. In diabetic animals, however; both perindopril and bosentan significantly reduced albuminuria and lowered elevated SBP. In addition both drugs improved creatinine clearance and relaxant response to ACh to a large extent. Perindopril was more potent with regard to the hypoalbuminuric effect and the effect on creatinine clearance, while bosentan-induced improvement of vascular reactivity to ACh was more significant. Different potencies of perindopril and bosentan in affecting certain studied parameters suggests that the two drugs work either through different mechanisms or through similar pathways but to different extents. The renoprotective and antiangiopathic effects of both drugs were independent of the blood glucose level because this parameter was not significantly altered by either treatment. In conclusion, it seems that both angiotensin II and endothelins play an important role in the pathogenesis of diabetic angiopathy and nephropathy with probable interaction between the two systems to augment the production of such pathological disorders. Therefore, ACELs and ET receptor antagonists are highly recommended in the management of diabetic and ET receptor antagonists are highly recommended in the management of diabetic complications

Protective effect of thymus extract against stress-induced gastric ulcer in rats

This study was conducted to investigate the protective effect of thymus extract against peptic ulcer in stress-induced gastric ulcer model in rats, together with the determination of its effect on gastric secretion. The possible effect of thymus extract on the isolated fundal strip of rat stomach and the isolated smooth muscle of guinea pig ileum was also studied. The oral administration of thymus extract [50 mg/kg/day] for one week significantly reduced the incidence of ulceration, the mean ulcer score and the ulcer index compared with the saline control group and achieved a preventive index of 57%. Also, it decreased gastric acidity, as it significantly reduced the mean pepsin concentration as compared with the saline control animals. On the other hand, thymus extract produced a dose- dependent relaxant effect on the isolated smooth muscle of guinea pig ileum, but not the isolated fundal strip of rat stomach