• Asma Shaukat
  • Naila Abrar
  • Ayesha Naureen
  • Muhammad Nawaz


Background: The use of beta blockers is limited by their ability to produce bronchospasm in asthmatics. Third generation β-blockers like Nebivolol may show better tolerability because they may augment the release of nitric oxide (NO) from endothelial cells. However the involvement of NO in the respiratory effect of Nebivolol remains controversial. The present study, carried out on isolated tracheal muscle strips of guinea pigs, was designed to explore this controversy. Method: Varying concentration of histamine ranging from 10‑7 M to 10‑3 M were used to plot a concentration response curve on the isolated tracheal muscle strips of guinea pig and was used as a control. The same concentration response curve was plotted in presence of a fixed concentration of Nebivolol 10-6 M and then again in presence of a fixed concentration of L-Nitro Arginine Methyl Ester (L-NAME) 10-4 M and Nebivolol 10-6 M together in a series of experiments using six sets of isolated tracheal muscle strips in each case. Results: Nebivolol did not produce any significant shift in the concentration response curve while in the presence of L-NAME, Nebivolol shifted the histamine concentration response curve upwards and to the left. Conclusion: Nebivolol does not augment the histamine induced contraction of respiratory smooth muscle of guinea pig but in the presence of Nitric Oxide inhibitor L-NAME a significant augmentation of the same curve occurs, indicating a role of NO in the sparing of respiratory smooth muscle by Nebivolol.Keywords: Nebivolol, L-NAME, Concentration response curve, Tracheal muscle


Dal Negro R. Pulmonary effects of nebivolol. Ther Adv Cardiovas Dis 2009;3:329–34.

Scheen AJ. Pharma-clinics medication of the month, nebivolol Rev Med Liege 2001;56:788–91.

Bundkirchen A, Brixius K, Bölck B, Nguyen Q, Schwinger RH. Beta 1-adrenoceptor selectivity of nebivolol and bisoprolol. A comparison of [3H]CGP 12.177 and [125I] iodocyanopindolol binding studies. Eur J Pharmacol 2003;460:19–26.

Matera MG. Nitric oxide and airways. Pulm Pharmacol Ther 1998;11:341–8.

Dal Negro RW, Tognella S, Pomari C. Once daily nebivolol does not reduce airway patency in patients with COPD and arterial hypertension. Clin Drug Invest 2002;22:361–7.

Clini E, Bianchi L, Pagani M, Ambrosino N. Endogenous nitric oxide in patients with stable COAD: Correlates with severity of disease. Thorax 1998;53:881–3.

Agostino BD, Gallelli L, Falciani M, Fici F, Mangrella M. Nebivolol and airway responsiveness in the rabbit. Life Sci 2001;68:2159–68.

Quang TT, Rozec B, Audigane L, Gauthier C. Investigation of the different adrenoceptor targets of nebivolol enantiomers in rat thoracic aorta. Br J Pharmacol 2009;156:601–8.

Gillani AH, Khan AU, Rauf M, Ghayur MN, Siddiqui BS, Wohra W, et al. Gastrointestinal selective airway and urinary bladder relaxant effect of Hyoscyamus niger are mediated through dual blockade of muscarinic receptors and calcium channels. Fundam Clin Pharmacol 2008;22:87–9.

Maffei A, Pardo AD, Carangi R, Carullo P, Poulet R, Gentile MT, et al. Nebivolol induces nitric oxide release in the heart through inducible nitric oxide synthase activation. Hypertension 2007;50:652–6.

De Clerck F, Van Gorp L, Loots W, Janssen PA. Differential effects of nebivolol, atenolol and propranolol on heart rate and on bronchoconstrictor responses to histamine in the guinea-pig. Arch Int Pharmacodyn Ther 1989;298:230–6.

Hoffman BB. Catecholamines, sympathomimetic drugs and adrenergic receptor antagonists. In: Brunton LL, Lazo JS, Parker KL (Eds). Goodman and Gillman’s. The Pharmacological Basis of Therapeutics. 11th ed. New York: Mc GrawHill; 2006. p. 215–68.

Maarsingh H, Leusink J, Zaagsma J, Meurs H. Role of the L-citrulline/L-arginine cycle in iNANC nerve-mediated nitric oxide production and airway smooth muscle relaxation in allergic asthma. Eur J Pharmacol 2006;546(1–3):171–6.

Ignarro LJ. Experimental evidences of nitric oxide-dependent vasodilatory activity of nebivolol, a third generation beta-blocker. Blood Press Suppl 2004;1:2–16.

Ricciardolo FL. Multiple roles of nitric oxide in the airways. Thorax 2003;58:175–82.




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