Abstract 14444: Differential Effects of Nebivolol vs Metoprolol Succinate on Sympathetic Vasoconstriction During Exercise in Hypertensive Patients
In normal physiologic states, sympathetic vasoconstriction is markedly blunted in exercising muscles to optimize blood flow to the metabolically active muscle. This phenomenon known as functional sympatholysis was shown to be mediated by nitric oxide (NO) and found to be impaired in the rodent model of angiotensin-induced hypertension via generation of oxidative stress, which inactivates NO. Recent studies from our laboratory confirmed presence of impaired functional sympatholysis in hypertensive patients during rhythmic handgrip exercise, resulting in augmented skeletal muscle ischemia. Nebivolol is a novel beta-adrenergic receptor blocker with NO releasing property. Whether nebivolol restores abnormal vascular function in hypertensive patients during exercise remains unknown. Therefore, we conducted studies in 20 hypertensive subjects in which we measured muscle oxygenation by near infrared spectroscopy and forearm blood flow (FBF) by Doppler ultrasonography in response to reflex increases in sympathetic nerve activity (SNA) evoked by lower body negative pressure (LBNP) at rest and during rhythmic handgrip exercise at 30% maximal voluntary contraction. These measurements were performed at baseline, after 12 weeks of nebivolol (5-20 mg/day), and after 12 weeks of metoprolol succinate (100-300mg daily), using a randomized crossover design. We found that nebivolol had no effect on LBNP-induced decreases in oxygenation and FBF in resting forearm (from -21.8 ± 5% to -18.0 ± 3% and from -27.4 ± 4% to -28.3 ± 4%, respectively; P > 0.05). However, nebivolol attenuated LBNP-induced reduction in oxygenation and FBF in exercising forearm (from -9.4 ±2% to -2.6 ± 2% and from -15.9 ±2% to -7.4 ± 2%, respectively, both p < 0.05 vs baseline). This effect of nebivolol on oxygenation and FBF in exercising forearm was not observed with metoprolol in the same subjects (-10.4 ± 2% and -12.3 ± 2%, respectively, both p > 0.05 vs baseline) despite similar reduction in resting BP. Nebivolol also had no effect on SNA at rest, during handgrip, or during handgrip plus LBNP, suggesting direct effect on vascular function. These data provide the evidence for nebivolol-induced restoration on functional sympatholysis in hypertensive humans, independent of BP reduction.
- © 2011 by American Heart Association, Inc.