Bedeutung des L-Arginin/NO-Systems für die Wirkung von Nebivolol

Zusammenfassung

β-Blocker vermitteln ihre Wirkung durch die Blockade von β-Adrenozeptoren; β-Blocker „erster Generation” blockieren nichtselektiv β₁- und β₂- Adrenozeptoren, β-Blocker „zweiter Generation” blockieren überwiegend nur β₁-Adrenozeptoren, β-Blocker „dritter Generation” haben zusätzliche vasodilatatorische Eigenschaften.

Nevibolol ist ist ein hochselektiver β₁-Adrenozeptor Blocker mit einer zusätzlichen vasodilatatorischen Wirkung, die durch das endotheliale L-Arginin/NO-System vermittelt wird. Dementsprechend führt es akut zu einer Senkung des peripheren Widerstandes, während β-Blocker erster/zweiter Generation (zumindest initial und passager) den peripheren Widerstand erhöhen. Außerdem führt Nebivolol zu einer Frequenzsenkung, die etwas geringer ausgeprägt ist als die von β-Blockern erster/zweiter Generation. β-Blocker gehören zur Standardtherapie der Hypertonie, der koronaren Herzkrankheit sowie der chronischen Herzinsuffizienz. Nebivolol sollte sich zur Therapie dieser Krankheiten gut eignen, da NO zusätzlich vasodilatatorisch und antiatherogen wirkt.

Die SENIORS-Studie hat gezeigt, dass Nebivolol bei älteren Patienten mit chronischer Herzinsuffizienz zu einer Verringerung der Morbidität und Mortalität führt. Zukünftige Studien sind notwendig, um die klinische Bedeutung der zusätzlichen über NO-vermittelten Wirkungen von Nebivolol zu klären und um heraus zu finden, ob Nebivolol in der Therapie der chronischen Herzinsuffizienz ähnlich wirksam ist wie die β-Blocker Metoprolol, Bisoprolol und Carvedilol.

Summary

β-Blockers exert their effects through blockade of β-adrenoceptors. First-generation β-blockers non-selectively block β1- and β2-adrenoceptors, while second-generation β-blockers predominantly block β1-adrenoceptors. Third-generation β-blockers possess additional vasodilator properties. Nebivolol is a highly selective b1-blocker with additional vasodilator effects which are mediated by the endothelial L-arginine/nitric oxide system. The hemodynamic action of nebivolol differs from those of first and second-generation β-blockers: it acutely cecreases peripheral resistance (while first and second-generation β-blockers cause an initial transient increase in peripheral resistance) and decreases in heart rate that are less pronounced than those evoked by first and second-generation β-blockers. β-blockers are frequently used in the treatment of hypertension, coronary artery disease and chronic heart failure. Nebivolol should thus be a suitable drug for treating these diseases, especially since nitric oxide has vasodilator and anti-atherogenic effects. One long-term trial (the SENIORS study) has shown that nebivolol, compared with a placebo, reduced death and hospital admission in elderly patients with chronic heart failure. Additional studies are needed to investigate the clinical relevance of nitric oxide-mediated vasodilatation and to show if nebivolol is as efficious as the other β-blockers - metoprolol, bisoprolol and carvedilol - in the treatment of chronic heart failure.

Schlüsselwörter

L-Arginin/NO-System - Nebivolol

Key words

L-arginine/nitric oxide system - nebivolol

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