Chronic Administration Of Angiotensin Research Articles

Angiotensin-(1–7) reduces proteinuria and diminishes structural damage in renal tissue of stroke-prone spontaneously hypertensive rats

Angiotensin (ANG)-(1-7) constitutes an important functional end-product of the renin-angiotensin-aldosterone system that acts to balance the physiological actions of ANG II. In the kidney, ANG-(1-7) exerts beneficial effects by inhibiting growth-promoting pathways and reducing proteinuria. We examined whether a 2-wk treatment with a daily dose of ANG-(1-7) (0.6 mg·kg(-1)·day(-1)) exerts renoprotective effects in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). Body weight, glycemia, triglyceridemia, cholesterolemia, as well as plasma levels of Na+ and K+ were determined both at the beginning and at the end of the treatment. Also, the weekly evolution of arterial blood pressure, proteinuria, and creatinine clearance was evaluated. Renal fibrosis was determined by Masson's trichrome staining. Interleukin (IL)-6, tumor necrosis factor (TNF)-α, and nuclear factor-κB (NF-κB) levels were determined by immunohistochemistry and confirmed by Western blotting analysis. The levels of glomerular nephrin were assessed by immunofluorescence. Chronic administration of ANG-(1-7) normalized arterial pressure, reduced glycemia and triglyceridemia, improved proteinuria, and ameliorated structural alterations in the kidney of SHRSP as shown by a restoration of glomerular nephrin levels as detected by immunofluorescence. These results were accompanied with a decrease in both the immunostaining and abundance of IL-6, TNF-α, and NF-κB. In this context, the current study provides strong evidence for a protective role of ANG-(1-7) in the kidney.

Neural control of the renal vasculature in angiotensin II-induced hypertension.

1. Chronic administration of angiotensin (Ang) II causes an increase in blood pressure via a multitude of actions, including direct vasoconstriction, hypertrophy and increased sympathetic nerve activity. In the present study, we assessed whether the hypertension resulting from chronic Ang II alters the ability of the renal vasculature to respond to sympathetic activity. 2. Angiotensin II was administered for 7 weeks via an osmotic minipump at a dose of 50 ng/kg per min, i.v., to a group of six rabbits. Blood pressure, measured at 0, 1, 2 and 6 weeks after insertion of the pump, increased from 76 +/- 2 to 104 +/- 6 mmHg at the end of 6 weeks, without any significant change in heart rate. The blood pressure in the control group remained constant at 76 +/- 2 mmHg. 3. After 7 weeks, rabbits were anaesthetized and the renal nerves were stimulated at 0.5, 1, 1.5, 2, 3, 5 or 8 Hz for 3 min at their supramaximal voltage (5.5 +/- 1.0 V in the normotensive group and 6.5 +/- 1.5 V in the hypertensive group) while the renal blood flow (RBF) response was recorded. Under anaesthesia, there was no difference in mean arterial pressure between the normotensive and hypertensive animals (77 +/- 2 and 80 +/- 7 mmHg, respectively). The resting RBF under these conditions was not significantly different in the hypertensive group (30 +/- 4 vs 26 +/- 5 mL/min in the normotensive vs hypertensive group, respectively). 4. Stimulation at increasing frequencies was associated with increasing reductions in RBF (e.g. 36 +/- 8% at 2 Hz in normotensive rabbits and 48 +/- 7% at 2 Hz in hypertensive rabbits). However, there were no significant differences between RBF responses in normotensive and hypertensive rabbits. 5. We conclude that hypertension associated with chronic Ang II administration does not alter the response in RBF to electrical stimulation of the nerves.

Effect of endothelin on myocardial fibrosis in response to chronic administration of angiotensin II or aldosterone

Effect of endothelin on myocardial fibrosis in response to chronic administration of angiotensin II or aldosterone

Chronic Administration of Angiotensin in Rats: Changes in Blood Pressure, Renal and Adrenal Histophysiology and Aldosterone Production12

Angiotensin II-amide in oil was administered subcutaneously to rats, in doses ranging from 0.05 to 0.4 mg per 100 g per day. At the highest dose there was marked histologic and histochemical evidence of increased secretory activity in the adrenal zona glomerulosa, together with a decline in the juxtaglomerular granulation index to zero by 4 weeks. Lower doses showed less severe changes. Animals receiving the largest dose were shown to have a steadily rising blood pressure during 11 days of injection. Adrenals obtained from these animals after injection for 2 weeks showed a detectable rise in ability to synthesize aldosterone in vitro.