Howard Florey Institute: Colleen Thomas

Dr Colleen Thomas

BSc (Hons) PhD (Mon)

Senior Research Officer
Systems Neurophysiology Group

Contact Details

Email:	colleen.thomas@florey.edu.au
Phone:	+61 (0)3 8344 0182
Fax:	+61 (0)3 9348 1707

Research Interests

Using an in vivo approach, I have made a substantial contribution to original lines of research focusing on the contributions of humoral factors (renal and cardiac) to cardiovascular function. Early work (Hons) focused on characterising the actions of the putative renal depressor substance, medullipin, in anaesthetised rabbits. Subsequent PhD and post-doctoral studies have examined the effect of the cardiac natriuretic peptides on neural control of the heart in normal health, with ageing and in hypertension. These cardiovascular reflex studies have been performed in awake, chronically instrumented, unstressed animals (rats and sheep). More recently, I have been investigating how flavonols protect the heart from myocardial infarction-reperfusion injury – especially in relation to reduced myocyte apoptosis and vascular remodelling (sheep).

A summary of my major findings that have had significant impact in the field includes

The elusive anti-hypertensive lipid substance from the renal medulla, “medullipin”, was demonstrated to not be platelet activating factor, nitric oxide or a prostanoid. The release and action of this substance was related to the level of renal hyperfusion (Pubs. 12-14, Rev. 1).
Atrial natriuretic peptide (ANP), and subsequently B-type natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), were demonstrated to selectively enhance autonomic reflexes originating from the heart itself, rather than from arterial baroreceptors. (Pubs. 2, 5, 7, 10).
The action of ANP on cardiac vagal afferent pathways to enhance reflex cardiac slowing was absent in spontaneously hypertensive rats unless they were treated with an angiotensin converting enzyme inhibitor to prevent the development of cardiac hypertrophy (Pubs. 9, 10)
Particulate guanylate cyclase natriuretic peptide receptors were discovered to be responsible for heart rate reflex actions of ANP (Pub. 4).
Impaired cardiac vagal reflexes as well as arterial baroreflex were demonstrated to be a feature of normal ageing. The deficit in cardiac reflexes with age could be improved with acute ANP infusion or by chronic neutral endopeptidase (NEP) inhibitor treatment. Of interest, NEP inhibition also improved arterial baroreflex function however we believe the mechanism for this effect could possibly be via adrenomedullin and not the natriuretic peptides (manuscripts in preparation).
Aged rats showed specific impairments of water intake in response to hypertonicity and hypovolemia, but not to injected angiotensin II, compared to young rats. Like aged humans, aged rats exhibited high plasma ANP levels, which may contribute to impairment of thirst with age (Pub. 1).

Current Studies

In anaesthetised animals, vagal neurotransmission is being measured by direct stimulation of the vagus nerve at increasing stimulus frequencies and measuring the reflex heart rate response. Frequency-response curves are being compared in old versus young rats with and without ANP infusion and in the presence or absence of NEP inhibitor.
Given evidence of ANP augmenting cardiac vagal reflex responsiveness, a post-hoc analysis of the differential responses of frequency components of heart rate to arterial pressure changes is being undertaken in data from conscious aged versus young rats in the absence and presence of ANP.
Towards unravelling the mechanism of action of natriuretic peptides on cardiac reflexes, we intend to measure natriuretic peptide receptors (via immunohistochemical and PCR methodologies) in heart and neural tissue (nodose and stellate ganglia) collected from young and aged rats.
Having shown significant reductions in infarct size and myocyte prevalence in flavonol-treated ovine hearts that experience 1h of ischaemia followed by a 3 h reperfusion period (unpublished data), we have now progressed from acute studies to recovery animals in order to assess the longer term effect of the drug on left ventricle structural changes (echocardiography) and myocyte apoptosis.
The anti-inflammatory actions of a novel drug in a model of balloon catheter injury in the carotid artery of rats are being examined.

Laboratory Techniques

Animal handling (large and small mammals)
Anaesthetic and surgical instrumentation for in vivo physiological recordings (conscious and anaesthetised animals).
Myocardial ischaemia-reperfusion and balloon catheter injury models
Electrophysiology
Hormone (radioimmunoassay) and electrolyte measurements
Immunohistochemistry
Western blot
PCR
Computerised planimetry
Fluorescent microspheres (regional blood flows)

Additional Information

Awards for Presentations

“Winifred G. Naylor Student Prize”
- International Society for Heart Research (Australasian Section Annual Meeting) - Best student presentation of a moderated poster, Auckland, New Zealand, August 1999
“Astra Young Investigator Award”
- High Blood Pressure Research Council of Australia (19th Annual Scientific Meeting) - Best Oral presentation in Fremantle, Perth, December 1997
"Early Career Investigator Poster Prize Finalist (for Clinical Science)"
- High Blood Pressure Research Council of Australia - 28th Scientific Meeting, Brisbane, December 2006

Manuscript Reviewer

Hypertension, Clinical and Experimental Pharmacology and Physiology, Protein and Peptide Letters

Publications and Articles

Please see PubMed.

Pub 1 McKinley MJ, Denton DA, Thomas CJ, Woods RL and Mathai ML. (2006). Differential effects of aging on fluid intake in response to hypovolemia, hypertonicity and hormonal stimuli in Munich Wistar rats. Proceedings of the National Academy of Sciences, 103 (9), 3450-3455.

Pub 2 Thomas CJ and Woods RL (2004). Do natriuretic peptides modify arterial baroreflexes? Experimental Physiology, 89, 709-715.

Pub 3 Thomas CJ and Woods RL (2003). Haemodynamic action of BNP substantially outlasts its plasma half-life in conscious dogs. Clinical and Experimental Pharmacology and Physiology. 30 (5/6), 369-375.

Pub 4 Thomas CJ and Woods RL. (2003). Guanylyl-cyclase receptors mediate cardiopulmonary vagal reflex actions of ANP. Hypertension, 41 (2), 279-285.

Pub 5 Thomas CJ, Allen, AM, McAllen, RM and Woods RL. (2002). ANP potentiates non-arterial baroreflex bradycardia: evidence from sino-aortic denervation in rats. Autonomic Neuroscience, 97 (2), 89-98.

Pub 6 Brunner-La Rocca HP, Woods RL, Thomas CJ, Kaye DM, Hastings J, Lambert E and Esler MD. (2002). Divergent effects of ANP and BNP in acute heart failure: evidence for a putative BNP-selective receptor? Journal of Hypertension, 20, 1195-1201.

Pub 7 Thomas CJ, May CN, Sharma AD and Woods RL (2001). ANP, BNP and CNP enhance bradycardic responses to cardiopulmonary chemoreceptor activation in conscious sheep. American Journal of Physiology, 280, R282-R288.

Pub 8 Thomas CJ, Head GA and Woods RL. (1999). Similar baroreflex bradycardic actions of atrial natriuretic peptide and B and C types of natriuretic peptides in conscious rats. Journal of Hypertension, 17, 801-806.

Pub 9 Thomas CJ, Head GA and Woods RL. (1998). ANP and bradycardic reflexes in spontaneously hypertensive rats: influence of cardiac hypertrophy. Hypertension, 32, 548 - 555.

Pub 10 Thomas CJ, Rankin AJ, Head GA and Woods RL. (1997). ANP enhances bradycardic reflexes in normotensive but not spontaneously hypertensive rats. Hypertension, 29, 1126-1132.

Pub 11 Grigg J, Kleinert S, Woods RL, Thomas CJ, Veraart P, Wilkinson JL and Robertson CF. (1996). Alveolar epithelial lining fluid cellularity, protein and endothelin-1 in children with congenital heart disease. European Respiratory Journal, 9 (7), 1381-1388.

Pub 12 Anderson WP, Woods RL, Thomas CJ, Szenazi G and Evans RG (1995). Renal medullary antihypertensive mechanisms. Clinical and Experimental Pharmacology and Physiology, Suppl. 2, S426-S429.

Pub 13 Thomas CJ, Anderson WP and Woods RL (1995). Nitric oxide inhibition does not prevent the hypotensive response to increased renal perfusion in rabbits. Clinical and Experimental Pharmacology and Physiology, 22 (5), 345-351.

Pub 14 Thomas CJ, Woods RL, Gao Y and Anderson WP. (1994). Pressure range for release of renomedullary depressor substance in rabbits Hypertension 23, 639-645.

Editorials / Reviews

Rev 1 Thomas CJ, Anderson WP, Woods RL, Alcorn D, Evans RG and Christy IJ. (1996). Evidence for a renomedullary vasodepressor hormone. Clinical and Experimental Pharmacology and Physiology, 23, 777-785.