Signal transduction, microgravity, cardiovascular, vascular disease, vascular smooth muscle
Included in "Who's Who in Frontier Science and Technology," 1983
Alumni Fellow, University of the Pacific, 1985
Silver Beaker Teaching Award, School of Medicine, UCI, 1993
Chancellor’s Award for Excellence in Undergraduate Research, for distinguished accomplishment in fostering undergraduate research, UCI, 2000
Excellence in Teaching, Office of Curricular Affairs, School of Medicine, UCI, 2004
Kaiser Permanente Award for Excellence in Teaching, Presented by the Associated Medical Students, School of Medicine, UCI, 2004
Dr. Purdy is a cardiovascular pharmacologist whose research addressed all aspects of neurotransmission in blood vessels. He is particularly interested in the properties of neurohumoral receptors that regulate vasomotion -- the dilation and constriction of blood vessels. Dr. Purdy used a variety of experimental techniques to characterize the second messenger processes associated with vascular receptors.
In addition to isometric contraction, changes in cytosolic calcium levels are detected simultaneously with contraction using calcium imaging in vessel rings loaded with the fluorescent calcium dye, Fura II. Biochemical second messengers mediating calcium mobilization and calcium sensitization are also assessed. These include the phosphoinositide metabolites, inositol trisphosphate and diacylglycerol and the Rho A/Rho kinase pathway. Novel tyrosine kinase second messengers are assessed using both Western analysis and immunoprecipitation followed by kinase activity assay. These methods are currently being applied to determine the mechanisms by which microgravity causes vascular hyporesponsiveness. The classical rodent hindlimb unweighting (HU) model is used to simulate microgravity and vessels are isolated from control and HU rats for in vitro analysis. Dr. Purdy and his group have shown that simulated microgravity increases the vascular expression of endothelial and inducible nitric oxide synthase. Consequently arteries are hyporesponsive to vasoconstrictor agents because they are exposed chronically to elevated nitric oxide.
Dr. Purdy and colleagues have also shown that simulated microgravity downregulates signaling through both tyrosine kinase and cyclooxygenase second messenger pathways. src, a tyrosine kinase, is an early signaling molecule in the pathways leading to the activation of two mitogen-activated protein kinases (MAPKs), extracellular receptor regulated kinase (ERK) and p38 MAPK. In turn, these MAPKs contribute to contraction by phosphorylating and, thereby, terminating inhibition of actin assembly/activation by caldesmon and heat shock protein 27, respectively. Thus, the HU-induced downregulation of src, ERK and p38MAPK also contribute to vascular hyporesponsiveness associated with simulated microgravity.
Smith, J.R., Kim, H., and Purdy, R.E.: Precontraction with elevated concentrations of extracellular potassium enables both 5-HT2A "Silent” receptors in rabbit ear. J. Pharmacol Exp Ther, 289: 354-360, 1999.
Sangha, D. Sara, Vaziri, N.D., Ding, Y., Purdy, R.E.: Vascular Hyporesponsiveness In Simulated Microgravity: Role of Nitric Oxide Dependent Mechanisms. J Applied Physiol, 88:507-517, 2000.
Chen, J., Yildiz, O., and Purdy R.E.: Phenylephrine Precontraction Increases the Sensitivity of Rabbit Femoral Artery to Serotonin by enabling 5-HT 1-like Receptors. J Cardio Pharm, 35:863-870, 2000.
Vaziri, N.D., Ding, Y., Sangha, D.S., and Purdy, R.E.: Upregulation of NOS by stimulated microgravity, potential cause of orthostatic intolerance. J Appl Physiol, 89:338-344, 2000.
Sangha, D., Han, S., Purdy, RE. Simulated microgravity upregulates an endothelial vasoconstrictor prostaglandin. J Applied Physiol, 91:789-796, 2001.
Ma, J., Kahwaji, J.I., Ni, Z., Vaziri, N.D., Purdy, R.E.: Effects of simulated microgravity on nitric oxide synthase expression and nitrate/nitrite content in different arteries of the rat. J Applied Physiol, 94:83-92, 2003.
Purdy RE, Wilkerson MK, Hughson RL, Norsk P, Watenpaugh DE. The cardiovascular system in microgravity: symposium summary. Proc West Pharmacol Soc. 2003;46:16-27.
Hwang S, Shelkovnikov SA, Purdy RE. Simulated microgravity effects on the rat carotid and femoral arteries: role of contractile protein expression and mechanical properties of the vessel wall. J Appl Physiol. 2007, 102:1595-603.
Summers SM, Ulloa AS, Purdy RE. Endothelial role in the thoracic aorta response to hindlimb unloading in rats. Aviat Space Environ Med. 2007,78:1103-7.
Shelkovnikov S, Summers SM, Elahimehr R, Adams G, Purdy RE, Vaziri ND. Effect of exercise training on aortic tone in chronic renal insufficiency. Am J Hypertens. 2008, 21:564-9.
Summers SM, Nguyen SV, Purdy RE. Hindlimb unweighting induces changes in the RhoA-Rho-kinase pathway of the rat abdominal aorta. Vascul Pharmacol. 2008, 48:208-14.
Society for Pharmacology and Experimental Therapeutics
American Association for the Advancement of Science
Pharmaceutical Sciences Council
American Heart Association, Circulation Council
Society for Experimental Biology and Medicine