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

• Published in: British journal of clinical pharmacology 2015-09, Vol.80 (3), p.425-435
• Main Authors: Mose, Frank H., Jensen, Janni M., Therwani, Safa, Mortensen, Jesper, Hansen, Annebirthe B., Bech, Jesper N., Pedersen, Erling B.
• Format: Article
• Language: English
• Subjects: Adrenergic beta-1 Receptor Antagonists - administration & dosage; Adrenergic beta-1 Receptor Antagonists - therapeutic use; Adult; Aged; arterial stiffness; blood pressure; Blood Pressure - drug effects; Blood Pressure Monitoring, Ambulatory; Clinical Trials; Cross-Over Studies; Double-Blind Method; essential hypertension; Female; fractional excretion of sodium; Glomerular Filtration Rate - drug effects; Humans; Hypertension - drug therapy; Hypertension - metabolism; Kidney Tubules - drug effects; Kidney Tubules - metabolism; Kidney Tubules - physiopathology; Male; Middle Aged; nebivolol; Nebivolol - administration & dosage; Nebivolol - therapeutic use; nitric oxide; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - biosynthesis; omega-N-Methylarginine - pharmacology; Treatment Outcome
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/bcp.12627

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.