Activity of Angiotensin‐Converting Enzyme After Treatment with L‐Arginine in Renovascular Hypertension

Abstract

The renin-angiotensin system plays a role in the pathophysiology of renovascular hypertension. In addition, some studies have demonstrated a beneficial effect of L-arginine (L-Arg), the precursor of nitric oxide (NO), in this model of hypertension. This study was designed to investigate the effects of L-Arg on cardiovascular parameters and on the activity of the angiotensin-converting enzyme (ACE), after 14 days of renovascular hypertension. The experiments were performed on conscious male Wistar rats. Two-kidney, one-clip renovascular hypertension (2KIC) was initiated in rats by clipping the left renal artery during 14 days, while control rats were sham-operated. One group was submitted to a similar procedure and treated with L-Arg (10 mg/ml; average intake of 300mg/day) from the 7th to the 14th day after surgery, whereas the respective control group received water instead. At the end of the treatment period, the mean arterial pressure (MAP) was measured in conscious animals. The rats were sacrificed and the ACE activity was assayed in heart and kidneys, using Hip-His-Leu as substrate. In a separate group, the heart was removed, the left ventricle (LV) was weighed and the LV/body weight ratios (LV/BW) were determined. We observed significant differences in MAP between the L-Arg-treated and untreated groups (129 +/- 7 vs. 168 +/- 6 mmHg; P< 0.01). The cardiac hypertrophy described for this model of hypertension was attenuated in the 2K1C-L-Arg-treated group (14th day, wet LV/BW: 2K1C-L-Arg = 1.88 +/- 0.1; 2K1C = 2.20 +/- 0.1 mg/g; P < 0.05). L-Arg administration caused an important decrease in cardiac ACE activity (2K1C-L-Arg: 118 +/- 15; 2K1C: 266 +/- 34 micromol/min/mg; P < 0.01). L-Arg also decreased the ACE activity in the clipped kidney by 47% (P < 0.01), but not in the nonclipped kidney. These data suggest that increased NO formation and reduced angiotensin II formation are involved in the anthihypertensive effect of orally administered L-arginine.

Simultaneous renal hypertension and type 2 diabetes exacerbate vascular endothelial dysfunction in rats

“…Accordingly, blunted contraction response to PE in the presence of l ‐NAME in this study indicates that these models are associated with reduced basal release of NO. This finding is similar to those of earlier reports (Gouvea et al. 2004; Crabos et al.…”

Development of renal atrophy in murine 2 kidney 1 clip hypertension is strain independent

“…The original model, which employed dogs, was one of accelerated hypertension, causing extensive damage to the contralateral kidney which was subjected to high blood pressure. In other species, including rats and mice, the animals do not develop malignant hypertension—the stenotic kidney develops progressive fibrosis and atrophy, whereas the contralateral kidney develops compensatory enlargement (Chade et al, 2003; Cheng et al, 2009; Eng et al, 1994; Gouvea et al, 2004; Thone-Reineke et al, 2003). Systemic activation of the renin-angiotensin-aldosterone system is essential for the early development of hypertension in this model (Basso and Terragno, 2001; DeForrest et al, 1982).…”

Role of Renal Nerves in the Treatment of Renovascular Hypertensive Rats withL-Arginine

“…The presence of a precursor of NO alone increased water and sodium excretion, and when associated with renal denervation, it induced an even greater water and sodium excretion. Previous studies in our laboratory demonstrated that, in the context of renovascular hypertension, L -arg treatment decreases the arterial pressure not only because of the already known vasodilator effects of NO formation but also because there is an increase in the renal excretion of water and sodium [ 40 ].…”