This Article Full Text Full Text (PDF) All Versions of this Article: 44/3/305    most recent 01.HYP.0000137983.45556.6ev1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by McEniery, C. M. Articles by Cockcroft, J. R. Search for Related Content PubMed PubMed Citation Articles by McEniery, C. M. Articles by Cockcroft, J. R. Related Collections Cardiovascular Pharmacology Endothelium/vascular type/nitric oxide Other Vascular biology

(Hypertension. 2004;44:305.)
© 2004 American Heart Association, Inc.

Scientific Contributions

Nebivolol Increases Arterial Distensibility In Vivo

Carmel M. McEniery; Matthias Schmitt; Ahmad Qasem; David J. Webb; Alberto P. Avolio; Ian B. Wilkinson; John R. Cockcroft

From the Clinical Pharmacology Unit (C.M.M., I.B.W.), University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK; Graduate School of Biomedical Engineering (A.Q., A.P.A.), University of New South Wales, Sydney, Australia; Department of Cardiology (M.S., J.R.C.), Wales Heart Research Institute, Cardiff, UK. Centre for Cardiovascular Science (D.J.W.), University of Edinburgh, Western General Hospital, Edinburgh, UK.

Correspondence to Dr C M McEniery, Clinical Pharmacology Unit, University of Cambridge, Addenbrooke’s Hospital, Cambridge CB2 2QQ, UK. E-mail cmm41{at}cam.ac.uk

Arterial stiffness is a key determinant of cardiovascular risk in hypertensive patients. ß-Blockers appear to be less effective than other drugs in improving outcome in hypertensive patients, and a potential explanation may be that ß-blockers are less effective in reducing arterial stiffness. The aim of this study was to assess the direct effect of ß-blockade on pulse wave velocity (PWV), a robust measure of arterial distensibility, using a local, ovine, hind-limb model. In addition, we hypothesized that the vasodilating ß-blocker nebivolol, but not atenolol, would increase arterial distensibility in vivo. All studies were conducted in anesthetized sheep. PWV was recorded in vivo using a dual pressure-sensing catheter placed in the common iliac artery. Intraarterial infusion of nebivolol reduced PWV by 6±3% at the higher dose (P<0.001), but did not alter mean arterial pressure (change of –1±3 mm Hg, P=0.1). In contrast, atenolol had no effect on PWV (P=0.11) despite a small drop in mean pressure (change of –5±3 mm Hg, P<0.01). Infusion of glyceryl trinitrate led to a dose-dependent fall in PWV, and 2 nmol/min produced a similar reduction in PWV to the higher dose of nebivolol (500 nmol/min). The effect of nebivolol on PWV was significantly attenuated during coinfusion of N^G-monomethyl-L-arginine (P=0.003) and also during coinfusion of butoxamine (P=0.02). These results demonstrate that nebivolol, but not atenolol, increases arterial distensibility. This effect of nebivolol is mediated through the release of NO via a ß₂ adrenoceptor–dependent mechanism. Thus, nebivolol may be of benefit in conditions of increased large artery stiffness, such as isolated systolic hypertension.

Key Words: blood pressure • nitric oxide • arteries • hemodynamics • receptors, adrenergic ß

This article has been cited by other articles:

				Q. CHE, M. J. SCHREIBER JR, and M. A. RAFEY Beta-blockers for hypertension: Are they going out of style? Cleveland Clinic Journal of Medicine, September 1, 2009; 76(9): 533 - 542. [Abstract] [Full Text] [PDF]

				P. M. Nilsson, P. Boutouyrie, and S. Laurent Vascular Aging: A Tale of EVA and ADAM in Cardiovascular Risk Assessment and Prevention Hypertension, July 1, 2009; 54(1): 3 - 10. [Full Text] [PDF]

				P. Lacolley, P. Challande, M. Osborne-Pellegrin, and V. Regnault Genetics and pathophysiology of arterial stiffness Cardiovasc Res, March 1, 2009; 81(4): 637 - 648. [Abstract] [Full Text] [PDF]

				C. L. Gray and U. A. Ndefo Nebivolol: A new antihypertensive agent Am. J. Health Syst. Pharm., June 15, 2008; 65(12): 1125 - 1133. [Abstract] [Full Text] [PDF]

				M. P Schneider, C. Delles, A. U Klingbeil, M. Ludwig, R. E Kolloch, M. Krekler, K. O Stumpe, and R. E Schmieder Effect of angiotensin receptor blockade on central haemodynamics in essential hypertension: results of a randomised trial Journal of Renin-Angiotensin-Aldosterone System, March 1, 2008; 9(1): 49 - 56. [Abstract] [PDF]

				H. Oberleithner, C. Riethmuller, H. Schillers, G. A. MacGregor, H. E. de Wardener, and M. Hausberg Plasma sodium stiffens vascular endothelium and reduces nitric oxide release PNAS, October 9, 2007; 104(41): 16281 - 16286. [Abstract] [Full Text] [PDF]

				A. Veverka, D. S Nuzum, and J. L Jolly Nebivolol: A Third-Generation {beta}-Adrenergic Blocker Ann. Pharmacother., July 1, 2006; 40(7): 1353 - 1360. [Abstract] [Full Text] [PDF]

				M. Schmitt, A. Avolio, A. Qasem, C. M. McEniery, M. Butlin, I. B. Wilkinson, and J. R. Cockcroft Basal NO Locally Modulates Human Iliac Artery Function In Vivo Hypertension, July 1, 2005; 46(1): 227 - 231. [Abstract] [Full Text] [PDF]