The study of renin-angiotensin-aldosterone in experimental diabetes mellitus

Abstract

It is generally accepted that hypertension and other vascular pathologies increase in diabetes mellitus (DM) patients as a result of the renin-angiotensin-aldosterone (RAA) system. In this study, changes in the renin-angiotensin-aldosterone (RAA) system level was determined in Streptozotocin (STZ)-injected rats. A total of 46 female Wistar albino rats (180-220 g body weight) was utilized in these experiments. STZ was given intraperitoneally to induce diabetes in rats. Streptozotocin (60 mg kg(-1) body weight) was dissolved in 0.1 m citrate--phosphate buffer (pH 4-5). The non-diabetic rats were injected with sterilized buffer alone to act as a control group. Blood glucose levels were 398+/-8.2 mg dl(-1), 488+/-11.75 mg dl(-1) and 658+/-29.6 mg dl(-1) at days 3, 12 and 30 respectively. The level of plasma renin activity (PRA) was measured as 7.69+/-1.07 ng ml(-1) h(-1); 1.82+/-0.22 ng ml(-1) h(-1) and 0. 67+/-0.12 ng ml(-1) h(-1) at days 3, 12 and 30, respectively. These values showed that the PRA levels are decreased with increased time period. Serum angiotensin converting enzyme (ACE, E.C. 3.4.15.1) levels were increased at days 12 and 30 (p<0.05 and p<0.005), whereas serum aldosterone levels were increased at days 3 and 12 (p<0.05). The level of urea and creatinine increased at days 12 and 30 (p<0.05 and p<0.005, respectively) when compared to the control group. The data from these experiments indicate that the PRA level decreased whereas ACE activity level increased in diabetic rats compared with the control. Aldosterone levels increased at the first stage of the experiment, but then decreased by the end of the experiment as a result of changes in renin and ACE levels.

The effects of captopril and losartan on erythrocyte membrane Na+/K+- ATPase activity in experimental diabetes mellitus

“…Other blood samples were collected in tubes with heparin for plasma ACE activity and creatinine levels. Blood samples were centrifuged at 3000 rpm for 15 min, plasma separated and stored at 2 208C until further use [3].…”

Aldosterone and the autocrine modulation of potassium currents and oxidative stress in the diabetic rat heart

“…As aldosterone levels may show temporal variation following STZ treatment ( Tomlinson et al ., 1992 ; Nakayama et al ., 1998 ; Ustundag et al ., 1999 ), we also examined the effects of spironolactone in cells from longer term diabetic rats. In this case, male rats were made diabetic (with 60 mg kg −1 STZ) 5–7 weeks prior to experiments, with a mean non‐fasting blood glucose concentration of 28.8±2.6 m M ( n =9), which is significantly ( P <0.0005) higher than in control rats (15.1±1.2, n =11).…”

“…Whereas elevation in plasma aldosterone in cardiac pathology seems established ( Nakayama et al ., 1998 ; Ustundag et al ., 1999 ; Jorde et al ., 2002 ; Hollenberg et al ., 2004 ; Struthers, 2004 ), the evidence for extra‐adrenal synthesis of aldosterone ( Slight et al ., 1999 ; Katada et al ., 2005 ; Wasywich et al ., 2006 ) is still controversial ( Emmett, 2006 ). Our results confirm that plasma levels of aldosterone are elevated in diabetic male rats (Figure 2).…”

Increased blood pressure in the offspring of diabetic mothers

“…For example, Sharifi et al (40) demonstrated increased ACE activity in kidney, heart, lung and aorta during the development of twokidney, one-clip hypertension in rats, suggesting an important role of local ACE in the development of hypertension. Furthermore, STZ-diabetic rats showed enhanced blood pressure accompanied by increases in serum ACE activity (46). Huang et al observed that diabetes produced an increase in blood pressure, specifically, in mice with genetically enhanced ACE activity (26).…”