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Amrita Ahluwalia
Professor of Vascular Pharmacology
Centre for Clinical Pharmacology

Contact Details:

a.ahluwalia@qmul.ac.uk

Amrita Ahluwalia obtained a BSc in Pharmacology from Bath University and undertook doctoral training at the William Harvey Research Institute. In the mid Nineties she worked at University College as a Lecturer before returning to the William Harvey where she is currently a Professor of Vascular Pharmacology.


Current research interests


Professor Ahluwalia's work focuses on mechanisms of vascular homeostasis in inflammation and particularly the role of the endothelium. Recent research areas include:

Effects of nitrite and nitrate on the cardiovascular system in health and disease.

In contrast to nitric oxide (NO), which has well-established, important effects in regulation of cardiovascular homeostasis, its oxidative metabolite nitrite has, until recently, been considered to be physiologically inert. However, this view of nitrite as an inactive metabolite simply reflecting nitric oxide synthase (NOS) activity has been radically revised over the past 5-7 years. Much evidence has now accumulated demonstrating that nitrite also serves as a storage form of NO. Moreover, that this nitrite store of NO is released preferentially under acidic and/or hypoxic conditions exerting a number of cytoprotective effects that limit the extent of damage caused by an ischemia/reperfusion [I/R] insult. We first demonstrated this phenomenon in the heart and many others have followed demonstrating protection against I/R injury in various organs including the liver, brain and kidney. We have been investigating the mechanisms involved in nitrite reduction and recently published evidence implicating two enzymes: xanthine oxidoreductase and eNOS. More recently, the vasodilator activity of nitrite has attracted much attention. In 2008 we published our findings that a dietary nitrate load, in the form of beetroot juice, reduced blood pressure and improved platelet and endothelial function in healthy volunteers. We are currently investigating the effect of a similar inorganic nitrate load in hypertensive and hypercholesterolemic patients.


Role of the kinin B1 receptor in cardiovascular disease.


We demonstrated in 1996 that the inducible kinin B1 receptor plays an integral role in neutrophil recruitment to a site of inflammation. Our research has focussed on the molecular pathways involved in this response and we have identified two particular pathways that play a role i.e. B1-induced endothelial chemokine generation and sensory C-fibre activation. Our most recent studies have demonstrated that laminar shear stress plays a major role in regulating endothelial kinin B1 receptor expression and that this regulation implicates the receptor in atherosclerosis.

 

Endothelium-derived hyperpolarising factor (EDHF) in cardiovascular protection and the influence of sex on its activity.

In 2005 we published our findings demonstrating that endothelium-dependent relaxation of the resistance arteries of females is predominantly mediated by the endothelial factor EDHF, whereas in the resistance vessels of males NO and the prostaglandin PGI2 are the primary endothelial factors. We also demonstrated that this propensity to express EDHF protected females from genetically-induced hypertension. In addition, our most recent findings demonstrate that sex-differences in acute inflammatory responses may have a role to play in the reduced susceptibility of females to cardiovascular disease. We are currently investigating the pathways involved in this sex-specific upregulation of EDHF and with collaborators at UCL we are also exploring the role of C-type- natriuretic peptide (CNP) as an EDHF in females. In addition, we are extending our investigations to healthy volunteers to determine the relevance of our findings in pre-clinical models to humans.

Investigation of the role of TRPV1 in vascular reactivity


In 2004 we identified a major role for the TRPV1 channel and sensory C-fibres in mediating the constriction of resistance arteries that occurs in response to rises in intraluminal pressure; termed myogenic tone. We are currently investigating the molecular pathways involved in this response. In addition we have demonstrated that 12-lipoxygnease products activate TRPV1 in the coronary vasculature and that the activity of these arachidonate metabolites results in cardioprotective actions as evidenced by decreases in I/R injury.


Key publications

  • Villar IC, Scotland RS, Khambata RS, Chan M, Duchene J, Sampaio AL, Perretti M, Hobbs AJ, Ahluwalia A. Suppression of Endothelial P-Selectin Expression Contributes to Reduced Cell Trafficking in Females: An Effect Independent of NO and Prostacyclin. Arterioscler Thromb Vasc Biol. 2011 31:1075-83.

  • Kapil V, Milsom AB, Okorie M, Maleki-Toyserkani S, Akram F, Rehman F, Arghandawi S, Pearl V, Benjamin N, Loukogeorgakis S, MacAllister R, Hobbs AJ, Webb AJ, Ahluwalia A. Inorganic nitrate supplementation lowers blood pressure in humans: role for nitrite-derived nitric oxide.  Hypertension.  2010, 56:274-281.

  • V Kapil, AJ Webb, A Ahluwalia. Inorganic nitrate and the cardiovascular system. 2010,  Invited Review Heart, 96, 1703-1709.

  • Duchene J, Cayla C, Vessillier S, Scotland R, Yamashiro K, Lecomte F, Syed I, Vo P, Marrelli A, Pitzalis C, Cipollone F, Schanstra J, Bascands JL, Hobbs AJ, Perretti M, Ahluwalia A (2009). Laminar shear stress regulates endothelial kinin B1 receptor expression and function: potential implication in atherogenesis. Arterioscler Thromb Vasc Biol. 11:1757-63.

  • Duchene J, Ahluwalia A. The kinin B(1) receptor and inflammation: new therapeutic target for cardiovascular disease. Curr Opin Pharmacol. Invited review 2009 Apr;9(2):125-31. Epub 2009 Jan 3. Review.

  • Webb AB, Rathod KS, Chu WL, Qureshi S, Lovell MJ, Lecomte FMJ, Perrett D, Raimondo C, Khoshbin E, Ahmed Z, Uppal R, Benjamin N, Hobbs AJ, Ahluwalia A. Mechanisms Underlying Erythrocyte and Endothelial Nitrite Reduction to Nitric Oxide in Hypoxia: Role for Xanthine Oxidoreductase and Endothelial Nitric Oxide Synthase. Circ Res. 2008, 103:957-96.

  • Webb AJ, Patel N, Loukogeorgakis S, Okorie M, Aboud Z, Misra S, Rashid R, Miall P, Deanfield J, Benjamin N, Macallister R, Hobbs AJ, Ahluwalia A. (2008). Acute Blood Pressure Lowering, Vasoprotective, and Antiplatelet Properties of Dietary Nitrate via Bioconversion to Nitrite. Hypertension. 51(3):784-90.

  • Johan Duchene, Florence Lecomte, Saleh Ahmed, Cecile Cayla, Joao Pesquero, Michael Bader, *Mauro Perretti & Amrita Ahluwalia (2007). A novel inflammatory pathway involved in leukocyte recruitment: role for the kinin B1 receptor and the chemokine CXCL5. J Immunol 179, 4849-4856.

  • Ramona Scotland, Melanie Madhani, Salvador Moncada, A.J.Hobbs & A. Ahluwalia. (2005). Endothelial nitric oxide synthase/cyclooxygenase-1 double knockout mice reveal cardioprotective role for endothelium-derived hyperpolarizing factor. Circulation, 111: 796-803.

 

 

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Research Staff:

  • Sven van Eijl
  • Kristen Bubb
  • Rayomand Khambata
  • Alex Milsom
  • Vanessa Pearl
  • Isabel Calvo Fuentes

PhD Students:

  • Suborno Ghosh
  • Vikas Kapil
  • Dan Jones
  • Shanti Velmurugan

 

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