Tachykinins and the cardiovascular system.
The tachykinin family of vasoactive peptides comprises the neuropeptides substance P, neurokinin A and neurokinin B, and the newly discovered endokinins and hemokinins. Their cardiovascular effects are predominantly mediated by the family of neurokinin receptors. This review summarises the most recent advances in understanding the effects of tachykinins on the vasculature, and summarises their therapeutic potential. Tachykinins stimulate plasma extravasation, particularly acting through neurokinin-1 receptors in an endothelium-dependent manner. They therefore play prominent roles in tissue oedema and inflammation (called neurogenic inflammation). Pro-inflammatory effects of tachykinins are enhanced by their capacity to stimulate inflammatory cell recruitment, and to initiate angiogenesis. Tachykinins also regulate vascular tone and blood flow, although differences between species and between different vascular beds make this a highly complex area of research. They may relax vessels in some scenarios whilst inducing vasoconstriction in other situations, the state of the endothelium appearing to be of key importance. Tachykinins also modulate blood pressure and heart rate, acting both peripherally, and on the central nervous system. Cardiovascular effects of tachykinins and neurokinin receptors may be important therapeutic targets in diverse disorders such as pulmonary oedema, hypertension, pre-eclampsia, complex regional pain syndrome type 2, stroke and chronic inflammatory diseases such as arthritis. Sophisticated modelling of human disease is required to enable neurokinin receptor antagonists to achieve this therapeutic potential.
Walsh
David A
DA
Division of Academic Rheumatology, University of Nottingham, Clinical Sciences Building, City Hospital, Nottingham, NG5 1PB, UK. david.walsh@nottingham.ac.uk
F McWilliams
Daniel
D
D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism; D002320:Cardiovascular Physiological Phenomena; D006801:Humans; D018039:Receptors, Tachykinin / Q000378:metabolism / Q000502:physiology*; D015320:Tachykinins / Q000378:metabolism / Q000502:physiology*
D018039:Receptors, Tachykinin; D015320:Tachykinins