1983 …2020

Research output per year

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Personal profile

Research interests

Heart-felt understanding of blood pressure and kidneys

The renin-angiotensin system is one of our most intricate hormone systems in the human body. It controls our blood pressure and fluid balance, and its effectiveness is vital to our kidney function. Dr Kate Denton says a better understanding of the renin-angiotensin system will lead to significant improvements in blood pressure control. By extension, Kate believes it is an important step in the fight against heart disease and earlier detection of kidney disease.




Hypertension and its associated complications affect men and women during different stages of their lives. Kate is focusing on what controls blood pressure in pregnant women, and what largely protects women from heart disease until menopause.

'One in 10 women experience hypertension during pregnancy,' Kate says. 'It's life-threatening for the mother and the child, and the only therapy we have at the moment is delivery. Blood pressure medication affects the baby, so you normally try to keep the pregnancy going for as long as possible without adversely affecting the mother. We're trying to understand what controls blood pressure during pregnancy.'

'Blood pressure is very different in how it's controlled in men and women. Females have lower blood pressure than males until menopause. Up until menopause, females are protected to a large extent from cardiovascular disease, but if you take the whole population, more women than men are affected. We want to understand why female hormones are protective and how they're helping to regulate blood pressure, and whether we can keep that protection going past menopause,' she says.

Kate says there's an intrinsic link between blood pressure and kidney disease. A healthy kidney consists of one million glomeruli, each of which filters a certain amount of blood, but patients often lose the majority of their kidney function before they have symptoms. Kate says it is important to understand how the individual filters work in order to detect kidney failure earlier.

'When you get down to between 25 and 50 per cent [glomeruli], you start to see signs of renal failure. We hope to work out how they're functioning, what's controlling them and work out methods of detecting renal damage earlier. Using a microscope and little glass pipettes about a micro in diameter at the tip, we can find a glomerulus, measure pressure and collect fluid in a single glomerulus and determine what's happening,' Kate says.

The method they use to do this is called renal micropuncture.

'If you're filtering, the blood pressure in those capillaries determines how much fluid moves across. In healthy glomeruli, pressure is normally kept constant by the constriction of blood vessels. I'm interested in what controls the pressure in those filters, and I can measure that with micropuncture.'

Kate is also exploring how the renal nerves, or sympathetic nerves, control our kidneys and blood pressure. She is using techniques to directly record and stimulate nerve activity.

'There's a lot of evidence in humans that suggests over-activity of the sympathetic nerves can change renal function and drive hypertension. One of the newest treatments for drug resistant hypertension is to sever the nerves around the kidney with laser surgery. I'm looking at how long it takes for nerves to regrow in the kidney once they have been severed,' Kate says.

'The amazing thing about these studies in humans is that they've followed the subjects for up to five years and blood pressure is being kept down significantly. Yet we know the nerves regrow, so what this suggests is that they connect to the tissues differently. Our studies aim to understand how this is occurring.'

 

Biography

Supervision interests

Research area keywords

  • Kidney
  • renin-angiotensin system
  • Hypertension
  • Renal Developmental Programming
  • renal sympathetic nerves
  • Pregnancy
  • dehydration

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Projects

Research Output

Fetal growth and well-being in a study of maternal hypertension in rabbits

Coombs, P., Walton, S., Maduwegedera, D., Flower, R. & Denton, K., 8 Jan 2020, (Accepted/In press) In : Anatomical Record. 11 p.

Research output: Contribution to journalArticleResearchpeer-review

Renal functional effects of the highly selective AT2R agonist, β-Pro7 Ang III, in normotensive rats

Hilliard Krause, L. M., Kemp, B. A., Tan, A. S. J., Jones, E. S., Del Borgo, M. P., Aguilar, M. I., Denton, K. M., Carey, R. M. & Widdop, R. E., 17 Apr 2020, In : Clinical Science. 134, 7, p. 871-884 14 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
File

The anti-fibrotic actions of relaxin are mediated through AT2R-associated protein phosphatases via RXFP1-AT2R functional crosstalk in human cardiac myofibroblasts

Wang, C., Pinar, A. A., Widdop, R. E., Hossain, M. A., Bathgate, R. A. D., Denton, K. M., Kemp-Harper, B. K. & Samuel, C. S., 16 Apr 2020, (Accepted/In press) In : The FASEB Journal. 17 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
File

AT1R-AT2R-RXFP1 functional crosstalk in myofibroblasts: Impact on the therapeutic targeting of renal and cardiac fibrosis

Chow, B. S. M., Kocan, M., Shen, M., Wang, Y., Han, L., Chew, J. Y., Wang, C., Bosnyak, S., Mirabito-Colafella, K. M., Barsha, G., Wigg, B., Johnstone, E. K. M., Hossain, M. A., Pfleger, K. D. G., Denton, K. M., Widdop, R. E., Summers, R. J., Bathgate, R. A. D., Hewitson, T. D. & Samuel, C. S., 1 Jan 2019, In : Journal of the American Society of Nephrology. 30, 11, p. 2191-2207 17 p.

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

Chronic low alcohol intake during pregnancy programs sex-specific cardiovascular deficits in rats

Walton, S. L., Tjongue, M., Tare, M., Kwok, E., Probyn, M., Parkington, H. C., Bertram, J. F., Moritz, K. M. & Denton, K. M., 22 Apr 2019, In : Biology of Sex Differences. 10, 1, 14 p., 21.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
File
4 Citations (Scopus)