Dr Angus M. Shaw
E: A.M.Shaw@gcal.ac.uk
Research Interests
One of the unique features of the pulmonary circulation is that it ensures optimal oxygenation of systemic arterial blood. This is achieved by directing blood to alveoli that are ventilated and by diverting blood away from alveoli that are unventilated. While the physiological mechanism(s) that underlie ventilation/perfusion-matching are poorly understood it is clear that some form of communication occurs between the alveoli and the small pulmonary arteries.
The pulmonary circulation contains two distinct arterial populations: conventional arteries (CA), which follow the airway branching pattern, and supernumerary arteries (SA) that arise from the CA at 90∞ and branch, without an accompanying airway, into the adjacent respiratory tissue. The origin of the SA may be specialised and has been suggested to be important in regulating blood flow into the SA and its associated alveolar capillaries. Therefore the recent discovery that each SA has an associated neurovascular bundle (NVB) that appears to form an anatomical link between the respiratory tissue and the region of the CA at the SA origin suggests that it may provide a communication pathway between the respiratory tissue and pulmonary arteries. The target tissue for these nerves appears to be the endothelium. A second finding is that cells resembling interstitial cells of Cajal (ICC) are present in the CA, situated between the endothelium and smooth muscle. That these cells make contact with the endothelial cells, endothelial nerves and possibly the smooth muscle cells suggests that they could conduct signals from the endothelium and/or endothelial nerves to the smooth muscle of the CA. Several recent reports have also identified vascular ICC-like cells in the same subendothelial location. ICC have been suggested to act as a pacemaker regulating rhythmic muscular contraction in smooth muscle of the gut and in lymphatic vessels. In pulmonary arteries rhythmic muscular contraction and relaxation (vasomotion) is selectively induced by the TXA2.
Ventilation-perfusion mismatching is the commonest cause of systemic hypoxaemia. Chronic hypoxaemia results in heart failure. A better understanding of the physiology of ventilation-perfusion matching may provide a more enlightened approach to the management of this clinical problem.
The aim of the project is to investigate role of the endothelium and ICCs in nerve-mediated responses in pulmonary arteries. The project will also investigate the role of ICC in mediating vasomotion.
Recent Research Publications
A. Tracey; V.R. Alapati; A. MacDonald; I.C. Wilkie; R.A. Davidson; A.D. Corbett; A.M. Shaw c-Kit-immunopositive cells in the subendothelium of bovine pulmonary arteries: morphological characteristics and role in vasomotion PA2 Vol1Issue3abst034P View
Tracey; A. MacDonald; R.A. Davidson; A.D. Corbett; I.C. Wilkie; A.M. Shaw Innervation of bovine pulmonary artery endothelium by nerve fibres arising from a supernumerary artery-associated neurovascular bundle PA2 Vol1Issue3abst035P View
Tracey, J. Irvine, D. Bunton, A. MacDonald, A.M. Shaw. Relaxation to bradykinin in bovine pulmonary supernumerary arteries : role of nitric oxide and a guanylyl cyclase. Br. J. Pharmacol Bristol 2002.
Tracey, D. Bunton, A. MacDonald, I. Wilkie, A.M. Shaw. Relaxation to bradykinin in bovine pulmonary supernumerary arteries can be mediated by both a nitric oxide -dependent and -independent mechanism. Br. J. Pharmacol (abs) Birmingham 2001) 113, 233P.
Tracey, A., MacDonald, A., & Shaw , A.M. (2002). Involvement of gap junctions in bradykinin-induced relaxation of bovine pulmonary supernumerary arteries before and after inhibition of nitric oxide guanylyl cyclase. Clin. Science. 103, 553-557.
Tracey, A., Bunton, D., Irvine, J., MacDonald, A., & Shaw, A.M. (2002). Relaxation to bradykinin in pulmonary supernumerary arteries can be mediated by both a nitric oxide-dependent and –independent mechanism. Br. J. Pharmacol., 137, 538- 557.
T. Brown, D. Bunton, A. MacDonald, A.M. Shaw. 5-HT1D-like receptor in bovine pulmonary supernumerary artery. Br. J. Pharmacol.(abs) Cambridge (2000).
T Brown, D Bunton, A MacDonald, J. Irvine, A.M. Shaw. The effect of tyrosine kinase and MAP kniase kinase inhibition on contractile responses to U46619 and 5-Hydroxytryptamine in bovine pulmonary supernumerary arteries. Br. J. Pharmacol (2001) 113 239P.
N. Brahmadevara, A.M. Shaw, A. MacDonald. Effects of endothelium and preconstriction on b-adrenoceptor-mediated relaxation in rat isolated aorta. Br. J. Pharmacol Bristol 2002.
N. Brahmadevara, A.M. Shaw, A. MacDonald.Lack of functional b3- or putative b4-adrenoceptors in rat isolated aorta. Br. J. Pharmacol Bristol 2002.
N. Brahmadevara, A.M. Shaw, A. MacDonald. Pharmacological differences between atypical b-adrenoceptors in rat aorta and b3-adrenoceptors in rat colon. Br. J. Pharmacol (2001) 134, 110P.
Lee Brawley, Angus M. Shaw, Allan MacDonald. b1-,b2- and atypical b-adrenoceptor-mediated relaxation in rat isolated aorta. Br. J. Pharmacol. (2000) 129, 637-644.
Lee Brawley, Angus M. Shaw, Allan MacDonald. Role of endothelium/nitric oxide in atypical b-adrenoceptor-mediated relaxation in rat isolated aorta. Eur. J. Pharmacology. (2000) 398, 285-296.
D. Bunton, A. MacDonald, T. Brown, A. Tracey, J.C. McGrath and A.M. Shaw. 5-Hydroxytryptamine-and U46619-mediated vasoconstriction in bovine pulmonary conventional and supernumerary arteries: effect of endogenous nitric oxide. Clin. Sci. (2000) 98, 81 - 89.
Bunton, D., MacDonald, A. Brown, T. & Shaw, A.M. Receptor subtypes from 5-hydroxytryptamine in bovine pulmonary conventional and supernumerary arteries. Br. J. Pharmacol. (1998) 125.
Bunton, D., MacDonald, A. & Shaw, A.M. Receptor subtypes for 5-HT in bovine pulmonary supernumerary arteries. Br. J. Pharmacol. (1977). Br. J. Pharmacol. (Edn.)
Bunton, D., Fisher, A., MacDonald, A., Montgomary, I., McGrath, J.C. & Shaw, A.M. Musculo-elastic structure of pulmonary supernumerary artery resembles a baffle valve. Am. J. Resp. Critical Care Med. 153 (4) A819. (1996).
Brown, C. & Shaw A.M. The effects of 5-hydroxytryptamine and selective agonists on contractile responses and cAMP in the first branch pulmonary artery of the rat. Am. J. Resp. Critical Care Med. 153 (4) A818. (1996).
Brawley, L. MacDonald, A. Shaw, A.M. The role of endothelium in atypical and classical B-adrenoceptor-mediated vasorelaxation in rat aorta. (1998) Br. J. Pharmacol. 125.
Angus M. Shaw, David C. Bunton, Tracy Brown, John Irvine, Allan MacDonald. Regulation of sensitivity to 5-hydroxytryptamine in pulmonary supernumerary but not conventional arteries by a 5-HT1D-like receptor. Eur. J. Pharmacol. (2000) 408, 69-82.
Angus M. Shaw, David C. Bunton, Alan Fisher, John C. McGrath, Ian Montgomery, Craig Daly and Allan MacDonald. V-Shaped cushion at the origin of bovine pulmonary supernumerary arteries: structure and putative function. J. Appl. Physiol. (1999) 87(6) 2348-2356.
Books
Shaw, A.M. & McGrath, J.C. (1996) Initiation of smooth muscle responses. In The Pharmacology of vascular smooth muscle (Garland & Angus, eds) Oxford University Press. ISBN 019 262387 7
Research Grants
Shaw. A.M. (1994). The regulation of pulmonary vascular resistance by supernumerary arteries and endothelial-derived vasoactive factors. Tenovus Scotland £4275
Shaw, A.M. (1994). The role of physical factors and neurohumoral agents in the regulation of conventional and supernumerary arteries in the pulmonary circulation. Wellcome Trust. £29,410.
Honours
British Pharmacological Society (Ordinary member)
PhD Students
Recent PhD Students
- Dr Tracey Brown
- Dr Arlene Tracey
Current PhD Student
- V.R. Alapati
Research Technician
- Mr J. Irvine