Role of Renal Nerves in the Treatment of Renovascular Hypertensive Rats with L

The purpose was to determine the role of renal nerves in mediating the effects of antihypertensive treatment with L-arginine in a renovascular hypertension model. The 2K1C (two-kidney one-clip model) hypertensive rats were submitted to bilateral surgical-pharmacological renal denervation. The animals were subdivided into six experimental groups: normotensive control rats (SHAM), 2K1C rats, 2K1C rats treated with L-arginine (2K1C + L-arg), denervated normotensive (DN) rats, denervated 2K1C (2K1C + DN) rats, and denervated 2K1C + L-arg (2K1C + DN + L-arg) rats. Arterial blood pressure, water intake, urine volume, and sodium excretion were measured. The 2K1C rats exhibited an increase in the mean arterial pressure (MAP) (from 106 ± 3 to 183 ± 5.8 mmHg, P<0.01), whereas L-arg treatment induced a reduction in the MAP (143 ± 3.4 mmHg) without lowering it to the control level. Renal nerve denervation reduced the MAP to normotensive levels in 2K1C rats with or without chronic L-arg treatment. L-arg and denervation induced increases in water intake and urine volume, and L-arg caused a significant natriuretic effect. Our results suggest that renal sympathetic activity participates in the genesis and the maintenance of the hypertension and also demonstrate that treatment with L-arg alone is incapable of normalizing the MAP and that the effect of such treatment is not additive with the effect of kidney denervation

Exercise training reduces cardiac dysfunction and remodeling in ovariectomized rats submitted to myocardial infarction.

The aim of this study was to evaluate whether exercise training (ET) prevents or minimizes cardiac dysfunction and pathological ventricular remodeling in ovariectomized rats subjected to myocardial infarction (MI) and to examine the possible mechanisms involved in this process. Ovariectomized Wistar rats were subjected to either MI or fictitious surgery (Sham) and randomly divided into the following groups: Control, OVX+SHAMSED, OVX+SHAMET, OVX+MISED and OVX+MIET. ET was performed on a motorized treadmill (5x/wk, 60 min/day, 8 weeks). Cardiac function was assessed by ventricular catheterization and Dihydroethidium fluorescence (DHE) was evaluated to analyze cardiac oxidative stress. Histological analyses were made to assess collagen deposition, myocyte hypertrophy and infarct size. Western Blotting was performed to analyze the protein expression of catalase and SOD-2, as well as Gp91phox and AT1 receptor (AT1R). MI-trained rats had significantly increased in +dP/dt and decreased left ventricular end-diastolic pressure compared with MI-sedentary rats. Moreover, oxidative stress and collagen deposition was reduced, as was myocyte hypertrophy. These effects occurred in parallel with a reduction in both AT1R and Gp91phox expression and an increase in catalase expression. SOD-2 expression was not altered. These results indicate that ET improves the functional cardiac parameters associated with attenuation of cardiac remodeling in ovariectomized rats subjected to MI. The mechanism seems to be related to a reduction in the expression of both the AT1 receptor and Gp91phox as well as an increase in the antioxidant enzyme catalase, which contributes to a reduction in oxidative stress. Therefore, ET may be an important therapeutic target for the prevention of heart failure in postmenopausal women affected by MI

Histological analysis of myocardial infarction area.

<p>Infarcted area analysis showing no differences among groups. Data are expressed as mean ± SEM (n = 7). *P<0.05.</p

Hemodynamic parameters eight weeks after myocardial infarction and exercise training in ovariectomized rats.

<p>Data are reposted as mean±SEM. HR, heart rate, SBP, systolic blood pressure, DBP, diastolic blood pressure and MAP, mean arterial pressure.</p>#<p> <i>P</i><0.05 vs Control;</p>†<p> <i>P</i><0.05 vs OVX+SHAM_ET;</p>‡<p> <i>P</i><0.05 vs OVX+SHAM_SED;</p>$<p> <i>P</i><0.05 vs OVX+MI_SED.</p><p>Hemodynamic parameters eight weeks after myocardial infarction and exercise training in ovariectomized rats.</p

Analysis of oxidative stress in cardiac tissue.

<p>Analysis of superoxide formation in sections of cardiac tissue by the dihydroethidium fluorescence. Representative images of Control (A), OVX+SHAM_SED (B), OVX+SHAM_ET (C), OVX+MI_SED (D) and OVX+MI_ET (E) groups. Data are expressed as mean ± SEM (n = 4). *P<0.05. Bar: 200 µm.</p

Cardiac function measurements.

<p>(A) Left ventricular systolic pressure (LVSP) demonstrating no differences among groups. (B) Exercise training reduced left ventricular end diastolic pressure (LVEDP) in OVX+MI_ET group compared to MI which occurs in parallel with an increased +dP/dt (C). There were a decrease in -dP/dt in the MI group compared with other groups which was not restored by ET (D). Data are expressed as mean ± SEM (n  =  12). *P<0.05.</p

Interstitial collagen deposition evaluation in rat hearts.

<p>Representative images of histological sections stained with Picrosirius of Control (A), OVX+SHAM_SED (B), OVX+SHAM_ET (C), OVX+MI_SED (D) and OVX+MI_ET (E) groups. Data are expressed as mean ± SEM (n = 7). *P<0.05. Magnifier 400x. Bar: 200 µm.</p

Myocyte cross sectional area evaluation.

<p>Representative images of histological sections stained with hematoxylin and eosin of Control (A), OVX+SHAM_SED (B), OVX+SHAM_ET (C), OVX+MI_SED (D) and OVX+MI_ET (E) groups. Data are expressed as mean ± SEM (n = 7). *P<0.05. Magnifier 400x. Bar: 50 µm.</p