Nebivolol reduces cardiac angiotensin II, associated oxidative stress and fibrosis but not arterial pressure in salt-loaded spontaneously hypertensive rats

Varagić, Jasmina; Ahmad, Sarfaraz; VonCannon, Jessica L; Moniwa, Norihito; Simington, Stephen; Brosnihan, Bridget; Gallagher, Patricia E.; Habibi, Javad; Sowers, James R.; Ferrario, Carlos M.

doi:10.1097/hjh.0b013e328356766f

Cited by 35 publications

(26 citation statements)

References 56 publications

(65 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A lower PRC would lead to a subsequent reduction in p‐AngII, which was also found in the present study. Our results are in accordance with observations from animal studies in which nebivolol reduced PRC and p‐Ang II in spontaneously hypertensive rats . Angiotensin II stimulates aldosterone secretion .…”

Section: Discussionsupporting

confidence: 92%

Effect of nebivolol on renal nitric oxide availability and tubular function in patients with essential hypertension

Mose

Jensen

Therwani

et al. 2015

Brit J Clinical Pharma

View full text Add to dashboard Cite

Aims Nebivolol is a selective β1‐receptor antagonist with vasodilating properties. In patients with essential hypertension, we tested the hypothesis that nebivolol increases systemic and renal nitric oxide (NO) availability using L‐NG‐monomethyl arginine (L‐NMMA) as an inhibitor of NO production. Methods In a randomized, placebo‐controlled, crossover study, patients with essential hypertension were treated with nebivolol for five days, along with a standardized diet and fluid intake. We examined the acute effects of systemic NO synthase inhibition with L‐NMMA on brachial blood pressure (bBP), pulse wave velocity (PWV) and central blood pressure (cBP) estimated by applanation tonometry, glomerular filtration rate (GFR), fractional excretion of sodium (FENa), urinary excretion of both aquaporin‐2 (u‐AQP2) and epithelial sodium channels (u‐ENaCγ), and plasma concentrations of nitrate/nitrite (p‐NOx) and vasoactive hormones after five days' treatment with placebo and nebivolol. Results Nebivolol significantly reduced PWV, bBP, cBP and plasma renin, angiotensin II and aldosterone concentrations. The renal parameters, p‐NOx and plasma arginine vasopressin concentration were not changed by nebivolol. There was no difference between nebivolol and placebo in the response to L‐NMMA, with LMMA inducing a similar increase in PWV, bBP and cBP and a similar decrease in GFR, uAQP2 and u‐ENaCγ and FENa [mean change −0.62% (95% confidence interval {CI} −0.40 to −0.84) during placebo vs. −0.57% (95% CI −0.46 to −0.68; P = 0.564) during nebivolol treatment]. Vasoactive hormones were changed to a similar extend by L‐NMMA during administration of nebivolol and placebo. Conclusions Nebivolol did not change p‐NOx, and inhibition of NO synthesis induced the same response in blood pressure, GFR, renal tubular function and vasoactive hormones during nebivolol and placebo. Thus, the data did not support the hypothesis that nebivolol changes vascular and renal NO availability in patients with essential hypertension.

show abstract

Section: Discussionsupporting

confidence: 92%

Effect of nebivolol on renal nitric oxide availability and tubular function in patients with essential hypertension

Mose

Jensen

Therwani

et al. 2015

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…However, there was a reversal when the hypertensive animals were treated with a beta-blocker, both for the sedentary and trained groups. Thus, beta-blocker treatment does seem to directly interfere with the amount of connective tissue in the heart, not only by reducing sympathetic activity but also by reducing the release of renin, plasma renin concentration, and thus the expression of cardiac angiotensin II (Varagic et al 2012). The increased myocardial fibrosis observed for the HS group relative to other groups was also observed in other studies that used other models of hypertension (Matsubara et al , 2006Hocher et al 1999;Saam et al 2003).…”

Section: Discussionsupporting

confidence: 59%

Treatment with nebivolol combined with physical training promotes improvements in the cardiovascular responses of hypertensive rats

Goessler

Martins‐Pinge

Bellinati

et al. 2014

Can. J. Physiol. Pharmacol.

View full text Add to dashboard Cite

The aim of this study was to determine whether exercise training combined with beta-blocker treatment promotes additional cardiovascular benefits compared with either intervention on its own. For this we used 76 Wistar rats distributed among different groups: normotensive sedentary (NS), normotensive trained (NT), normotensive sedentary treated with beta-blocker (NS_BB), normotensive trained treated with beta-blocker (NT_BB), hypertensive sedentary (HS), hypertensive trained (HT), hypertensive sedentary treated with a beta-blocker (HS_BB), and hypertensive trained rats treated with beta-blocker (HT_BB). Exercise training consisted of 4 weeks of swimming for 60 min a day, 5 days a week. Hypertension was induced with l-NAME (4 weeks), whereas the control rats received saline, and both the control and test rats received nebivolol. The animals underwent surgery to directly record their blood pressure. The HS group showed higher mean arterial pressure (MAP) (P = 0.000), systolic arterial pressure (P = 0.000), and diastolic arterial pressure (P = 0.000) compared with NS. MAP was higher in the HS compared with the HT (P = 0.002), HS_BB (P = 0.018), and HT_BB (P = 0.015) groups. Hearts from the HS group had a higher percentage of collagen compared with the NS and HS_BB groups. The HT_BB and HT groups only had a higher percentage of cardiac collagen by comparison with the HS_BB group. The HT_BB group showed higher levels of macrophages and neutrophils by comparison with the HT and HS_BB groups. Thus, treatment with a beta-blocker combined with physical training was associated with increased cardiovascular benefits over either intervention alone.

show abstract

“…Previous studies have demonstrated that treatment with nebivolol reduces plasma renin and angiotensin II levels in spontaneously hypertensive rats. 29,30 Moreover, nebivolol prevents the development of the arterial hypertension induced by chronic NO deficiency partially due to the inhibition of the renin-angiotensin system. 8 Sympatholytic actions of nebivolol have been previously described both in experimental animals and healthy subjects.…”

Section: Discussionmentioning

confidence: 99%

Enantioselective pharmacokinetics and cardiovascular effects of nebivolol in L-NAME hypertensive rats

et al. 2013

View full text Add to dashboard Cite

The cardiovascular effects and pharmacokinetics of nebivolol were assessed in N(G)-nitro-l-arginine methyl ester (L-NAME) hypertensive and normotensive control rats. Male Wistar rats were randomly divided to drink tap water (control) or L-NAME solution for 2 weeks. The effects of nebivolol (3 or 10 mg kg(-1) i.v.) on blood pressure (BP), heart rate and BP variability (BPV) were recorded in awake L-NAME and control rats. Short-term and beat-to-beat BPV was assessed by the s.d. and spectral analysis of the BP recordings. Nebivolol pharmacokinetics was studied by means of traditional blood sampling. Nebivolol showed enantioselective pharmacokinetics in both experimental groups; the clearance and the volume of distribution of l-nebivolol were significantly greater than those of the d-enantiomer. The hypotensive response to nebivolol was significantly enhanced in L-NAME rats (Δmean arterial pressure (MAP): -16.1±1.1%, P<0.05 vs. control rats) compared with normotensive animals (ΔMAP: -1.4±2.1%). An analysis of the beat-to-beat BPV showed a greater reduction in VLF BPV in the L-NAME compare with the control rats. Nebivolol significantly reduced the low-frequency/high-frequency ratio in hypertensive L-NAME animals compared with normotensive rats. Short-term BPV was markedly reduced by nebivolol in both experimental groups, although the attenuation of the s.d. of BP recording was greater in L-NAME rats. In conclusion, the hypotensive efficacy of nebivolol is significantly enhanced in L-NAME rats compared with normotensive animals, which is most likely due to a greater reduction in vascular sympathetic activity. Nebivolol markedly attenuated short-term BPV in both experimental groups, suggesting that β-blockers with additional pharmacological actions provide beneficial cardiovascular effects by controlling high BP and its short-term variability.

show abstract

Nebivolol reduces cardiac angiotensin II, associated oxidative stress and fibrosis but not arterial pressure in salt-loaded spontaneously hypertensive rats

Cited by 35 publications

References 56 publications

Effect of nebivolol on renal nitric oxide availability and tubular function in patients with essential hypertension

Effect of nebivolol on renal nitric oxide availability and tubular function in patients with essential hypertension

Treatment with nebivolol combined with physical training promotes improvements in the cardiovascular responses of hypertensive rats

Enantioselective pharmacokinetics and cardiovascular effects of nebivolol in L-NAME hypertensive rats

Contact Info

Product

Resources

About