Effects of a PPAR-gamma receptor agonist and an angiotensin receptor antagonist on aortic contractile responses to alpha receptor agonists in diabetic and/or hypertensive rats.

AIM: The aim of this study was to investigate the effects of pioglitazone and losartan pre-treatment on the aortic contractile response to the alpha-1 agonist, phenylephrine, and the alpha-2 agonist, clonidine, in L-NAME-induced hypertensive, STZ-induced diabetic, and hypertensive diabetic rats. METHODS: Male Wistar rats were randomly allocated to four groups: control, diabetic (DM), hypertensive (HT) and hypertensive diabetic (HT + DM) groups. Three weeks after drug application, in vitro dose-response curves to phenylephrine (Phe) (10-9-10-5 M) and clonidine (Clo) (10-9-10-5 M) were recorded in aortic rings in the absence (control) and presence of pioglitazone (10 µM) and/or losartan (10 µM). RESULTS: Pioglitazone and losartan caused a shift to the right in contractile response to phenylephrine in all groups. The sensitivity of the aortic rings to phenylephrine was decreased in the presence of pioglitazone and/or losartan in all groups. The contractile response of clonidine decreased in the presence of pioglitazone and/or losartan in the control, HT and DM groups. CONCLUSION: The sensitivity of aortic rings to alpha-1 and alpha-2 adrenoceptors was decreased in the presence of pioglitazone and/or losartan in diabetic and hypertensive rats. Concomitant use of PPAR-gamma agonists, thiazolidinediones, and angiotensin receptor blockers may be effective treatment for diabetes and hypertension.

Effects of angiotensin converting enzyme inhibition on adiponectin levels and lipid profile in the ovariectomized-aged rats.

OBJECTIVE: To investigate the relationship between angiotensin converting enzyme (ACE) and adiponectin and lipid profile in the ovariectomized-aged rats. MATERIALS AND METHODS: Wistar albino rats were first divided into two groups; control (C) and ovariectomized (OVX). Bilateral ovariectomy were carried out on rats (n = 30) except control group (n = 10). After 6 weeks from ovariectomy, ovariectomized rats were subdivided into three groups; one group received no treatment (OVX), two groups received low dose (OVX + Cap5; 5 mg/kg/day) and high dose (OVX + Cap20; 20 mg/kg/day) captopril (Cap). Body weights were monitored weekly. Adiponectin, triglyceride, cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and very low density lipoprotein cholesterol (VLDL-C) levels were measured at the end of the 6 weeks. RESULTS: In the OVX group, body weights increased (P < 0.001). In the OVX + Cap20 group, body weights significantly decreased compared with the OVX group during weeks 5 and 6 (P < 0.05). While adiponectin levels increased in the OVX + Cap5 group (P = 0.014), triglyceride and cholesterol levels decreased in the OVX + Cap20 group (P = 0.016 and P < 0.001, respectively) compared to the OVX group. HDL-C and VLDL-C levels decreased only in OVX + Cap20 group (P < 0.005). CONCLUSIONS: ACE inhibitors may be decreasing the ovariectomy-induced weight gain by increasing adiponectin levels, and by affecting lipid profiles. The adipose tissue renin-angiotensin system (RAS) may be playing an important role in the development of adiposity.

Silymarin improves vascular function of aged ovariectomized rats.

Both aging and estrogen depletion lead to endothelial dysfunction, which is the main reason of many cardiovascular diseases. Previous reports have shown that cell protective effect of silymarin (SM) depends on its antioxidant and phytoestrogenic properties. We investigated the effect of SM on vascular stiffness of aged menopausal rats and the involvement of estrogenic activity in this effect. Isolated rat aortas were obtained from 22-month-old rats, after 18 months of ovariectomy (OVX) follow-up. Each ring was incubated in tissue bath either with SM (50 mg/L) and 17ß-estradiol (10 µM, E2) or in the presence of SM/fulvestrant (50 mg/L, 10 µM). Endothelium-intact rings were precontracted with phenylephrine (0.001-30 µM) or high potassium (40 mM); endothelium-dependent/independent relaxant responses were obtained using acetylcholine (0.001-30 µM) and sodium nitroprusside (0.0001-3 µM), respectively. While phenylephrine sensitivity was significantly increased in OVX rats, relaxations were significantly less in aged OVX rats compared with young rats. In spite of the presence of estrogen antagonist, immediate SM treatment restored the endothelial function and vascular tone better than estrogen replacement. Additionally, as a complementary and alternative medicine, it does not cause estrogenic side effects when taken acutely.

The effect of Hypericum perforatum (St. John's Wort) on experimental colitis in rat.

The aim of the present study was to investigate the effect of Hypericum perforatum (HP) on the inflammatory and immune response of colonic mucosa in rat with induced inflammatory bowel disease and that on various enzyme activities in blood and bowel tissue. Male Wistar albino rats were divided into three main groups: control, third day, and seventh day of colitis. Third-day and seventh-day groups were divided into four subgroups. Colitis was induced in all groups except the control group by 2,4,6-trinitrobenzene sulfonic acid (TNBS). The colitis group received saline; treatment groups received HP extract (50, 150, and 300 mg/kg/day, respectively). Glutathione (GSH), catalase (CAT), and malondialdehyde (MDA) activities in blood were measured. Catalase, myeloperoxidase (MPO), glutathione peroxidase (GSH-Px), glutathione reductase (GR), malondialdehyde, and nitric oxide (NO) activities were measured from tissue samples. Colonic damage was significantly reduced by HP extract. Macroscopic scoring of colonic damage significantly reduced in groups given HP extract compared with in the colitis group (P < 0.001). Blood catalase levels were reduced in the HP (150 mg/kg/day) compared with the colitis group (P < 0.01). Blood GSH levels significantly increased in groups treated with HP compared with control (P < 0.001) on the third and seventh day. Tissue GR levels reduced in the colitis and HP (50 mg/kg/day) groups compared with control (P < 0.05). Tissue MPO activity increased in the colitis and treatment groups compared with control (P < 0.007). GSH-Px levels increased in the colitis group compared with control at day 3 (P = 0.006). HP has a protective effect on TNBS-induced inflammatory bowel disease (IBD), probably due to an anti-inflammatory and antioxidant mechanism.