Cupples, Will - Simon Fraser University - Department of Biomedical Physiology and Kinesiology

研究领域

High blood pressure is the single most important cause of kidney disease. So we need to understand how the kidney normally is protected from episodes of high blood pressure. In relation to their size the two kidneys have the highest blood flows in the body (1% of body mass receives 20% of cardiac output). A human kidney contains a million functional units called nephrons. Each nephron consists of a glomerulus, the tiny filter where fluid is removed from blood, and the tubule that leads fluid away. The glomerulus is a delicate structure and must be protected from episodes of high blood pressure that occur routinely in all of us. Humans and other animals have a process that adjusts the caliber of the small blood vessels that feed the glomeruli. The process is called autoregulation because it occurs entirely within the kidney. It stabilizes kidney blood flow and pressure at the glomerulus when blood pressure varies. Typically it is thought that autoregulation at each glomerulus acts independently. However, neighboring nephrons (about 20 in a cluster) exchange information and tend to work together. We suspect that these interactions are important to the effectiveness of autoregulation but we really know very little about them. We acquire images of perfusion at the surface of the kidney and analyze them to examine the signatures left when autoregulation is active. This will tell us how important it is for the nephrons in a cluster to work together. We will define how big the cluster is and how its size varies under normal conditions. Then we will use several experimental tricks to change the number of nephrons in the cluster. We expect that autoregulation provides better protection when nephrons act together. Another goal of this project is to determine how the size of the clusters is governed by blood pressure and how it is regulated by two potent vasoactive compounds that are made, act, and metabolized within the kidney. These are of course angiotensin II and nitric oxide. We are funded by CIHR and have a team made up of a physiologist (Cupples), a kidney doctor (B Braam, Univ of Alberta), and an engineer who specializes in data analysis (KH Chon Worcester Polytechnic Institute).

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Mitrou NGA, Cupples, WA. Renal blood flow dynamics in inbred rat strains provide insight into autoregulation. Current Vascular Pharmacology 2013, in press. Scully CG, Mitrou N, Braam B, Cupples WA, Chon KH. Detecting physiological systems with laser speckle perfusion imaging of the renal cortex. Am J Physiol Regul Integr Comp Physiol 2013; 304: R929-39. doi:10.1152/ajpregu.00002.2013. Scully CG, Siu KL, Cupples WA, Braam B, Chon KH. Time-frequency approaches for the detection of interactions and temporal properties in renal autoregulation. Ann Biomed Eng 2013; 41: 172-84. DOI: 10.1007/s10439-012-0625-1 Sima CA, Koeners MP, Joles JA, Braam B, Magil AB, Cupples WA. Increased susceptibility to hypertensive renal disease induced by type 1 diabetes mellitus is not modulated by salt intake. Diabetologia 2012; 55: 2246-55. (doi:10.1007/s00125-012-2569-2) Siu KL, Sung B, Cupples WA, Moore LC, Chon KH. Detection of low frequency oscillations in renal blood flow. Am J Physiol Renal Physiol 2009; 297: F155-62. Lau C, Sudbury I, Thomson M, Howard PL, Magil AB, Cupples WA. Salt-resistant blood pressure and salt-sensitive renal autoregulation in chronic streptozotocin diabetes. Am J Physiol Regul Integr Comp Physiol 2009; 296: R1761-70. Wang X, Loutzenhiser RD, Cupples WA. Frequency modulation of renal myogenic autoregulation by perfusion pressure. Am J Physiol Regul Integr Comp Physiol 2007; 293: R1199-1204. Cupples WA, Braam B. Assessment of renal autoregulation. Am J Physiol Renal Physiol 2007; 292: F1105-23. Shi Y, Wang X, Chon KH, Cupples WA. Tubuloglomerular feedback-dependent modulation of renal myogenic autoregulation by nitric oxide. Am J Physiol Regul Integr Comp Physiol 2006; 290: R982-91.