Chronic Administration Of Tempol Fails To Improve The Antihypertensive Response To Nebivolol In L-name Hypertensive Rats

SANTA CRUZ, DM; BERTERA, FM; POLIZIO, AH; TOMARO, ML; TAIRA, CA; HOCHT C; BALESTRASSE, KB

ORLANDO, FL

Congreso; HBRP 2011 convention; 2011

HBRP

We previously demonstrated that dual association between nebivolol-tempol improves the hypotensive response on normotensive animals. To further elucidate the mechanism of this association, we evaluated its antihypertensive response in N (G)-nitro-l-arginine methyl ester (L-NAME) hypertensive rats. Nebivolol, has higher b1-selectivity than others b-blockers and promotes periphery vasodilation mediated by endothelial nitric oxide synthase (eNOS), being this last enzyme highly dependent on oxidative stress status. The aim of this work was to study the antihypertensive effect of nebivolol and the association with tempol, a superoxide dismutase mimetic, in L-NAME hypertensive rats.Twenty-eight -Male Wistar rats (250-270 g) were divided into four groups; control group (C), rats treated with tempol (CT, 172 mg/ml in the drinking water during 7 days), rats treated with L-NAME (H, 400 mg/ml during 14 days) and rats treated with tempol plus L-NAME (HT, 172 mg/ml and 400 mg/ml, 7 and 14 days, respectively). At the seventh day, the carotid and the femoral artery were cannulated. Carotid artery was connected to a polygraph and the mean arterial pressure (MAP) and heart rate (HR) were recorded. After recovery, nebivolol was administrated via femoral vein into the C, CT, H and HT animals at a concentration of 3 mg/kg. Basal MAP was significantly higher in H rats (137 ± 2 mmHg, n = 7, P < 0.05) with regard to control rats (102 ± 7 mmHg). Nebivolol decreased MAP in H (MAP 119 mmHg ± 5.4, p<0.05 vs. baseline) but not in C animals. Chronic treatment with tempol neither modify MAP basal levels of C and H, nor the hypotensive response to nebivolol in HT rats (117.5 ± 4.0 mmHg) with respect to H animals treated with nebivolol. Also, no differences were found in basal HR between C and H rats (C: 365 ± 10 and H: 359± 10 bpm). On the other hand, nebivolol diminished equally HR in both H and HT groups (H: 298 ±20 vs HT: 301 ± 18 bpm). In conclusion, the enhanced hypotensive response to nebivolol found in L-NAME hypertensive rats suggests the compromise of sympathetic activity in this model of hypertension. Otherwise, the chronic administration of tempol fails to improve the antihypertensive effect of nebivolol when the NOS pathway is not operativ