Some effects of nipradilol, a beta-antagonist possessing a nitroxy group, on smooth muscle of the pig coronary artery

Br J Pharmacol. 1996 Apr;117(8):1707-15. doi: 10.1111/j.1476-5381.1996.tb15343.x.


1. The effects of nipradilol, a beta-adrenoceptor antagonist which possesses a nitroxy group, on cytosolic Ca2+ concentration ([Ca2+]i), and on tension development were simultaneously measured by front-surface fluorometry and fura-2-loaded strips in the proximal portion of pig coronary arteries. 2. Nipradilol reduced in a concentration-dependent manner both the [Ca2+]i and tension, irrespective of whether the strips were unstimulated or exposed to either high K+ or histamine containing solutions. However, both in the case of contractions induced by high K+-depolarization and histamine stimulation, for a given [Ca2+]i elevation the tension which developed in the presence of nipradilol was smaller than that generated in its absence, so that the [Ca2+]i-tension curves during the contraction were shifted to the right. 3. In the absence of extracellular Ca2+, the [Ca2+]i elevation due to the release of Ca2+ from histamine-sensitive store was inhibited by nipradilol. Nipradilol had no effect on the [Ca2+]i elevation due to the release of Ca2+ from caffeine-sensitive stores; however, it did inhibit the caffeine-induced increase in tension. A derivative of nipradilol, which lacked a nitroxy molecule (Nip(-N)), had no effect on the [Ca2+]i and tension elevated by histamine or caffeine in the absence of extracellular Ca2+. 4. The beta-adrenoceptor agonist, isoprenaline, reduced [Ca2+]i tension when applied to steady state contractions induced by high K+, or at the peak level of tension to histamine. The reduction of [Ca2+]i and tension induced by isoprenaline was inhibited by Nip(-N) in a concentration-dependent manner and nipradilol inhibited the isoprenaline-induced relaxation with bell-shaped concentration-response curves. At lower concentrations, nipradilol acted as a beta-blocker, the IC50- value being smaller than that of Nip(-N), and at higher concentrations, it acted as a nitrovasodilator. 5. Thus, it is suggested that, at lower concentrations, nipradilol, an antianginal drug, acts as a beta-adrenoceptor antagonist. At higher concentrations, it relaxes the proximal portion of the coronary artery by directly reducing [Ca2+]i and the Ca2+-sensitivity of the myofilaments, apparently due to the presence of the nitroxy molecule.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Adrenergic beta-Antagonists / chemistry
  • Adrenergic beta-Antagonists / pharmacology*
  • Analysis of Variance
  • Animals
  • Caffeine / pharmacology
  • Calcium / metabolism*
  • Central Nervous System Stimulants / pharmacology
  • Coronary Vessels / drug effects
  • Coronary Vessels / metabolism
  • Fluorescent Dyes / pharmacology
  • Fura-2 / pharmacology
  • Histamine
  • Isoproterenol / pharmacology
  • Muscle Contraction / drug effects*
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism
  • Propanolamines / chemistry
  • Propanolamines / pharmacology*
  • Swine


  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Central Nervous System Stimulants
  • Fluorescent Dyes
  • Propanolamines
  • Caffeine
  • Histamine
  • nipradilol
  • Isoproterenol
  • Calcium
  • Fura-2