How stress hormones change the daily rhythms of genes in the kidney arteries
With our funding, Dr Jess Ivy from the University of Edinburgh will investigate how steroid hormones can affect the daily rhythm of blood pressure so that we can try to reduce the risks in patients who are receiving these drugs.
Kidney patients often experience ‘non-dipping’
Our blood pressure has a daily rhythm, and in healthy individuals it is over 10% lower during the night than during the day. However, this night-time dip is reduced or absent in the majority of patients with chronic kidney disease or kidney transplants and this phenomenon is called ‘non-dipping’. Non-dipping has been linked with increased risk of heart and vessel disease and worsening kidney disease.
All of the cells of our body have a body clock, which ensures that our organs are ready for action when we are awake, and ready for repair and regeneration when we are asleep. Normally, steroid hormones produced by the body set the rhythms that keep our body clocks in time with our brain clock, which in turn keeps us in time with our external environment. Steroid hormones are important and effective drugs for treating inflammatory kidney disease and they are also used as part of immunosuppression therapy after transplant, but we know they can also cause non-dipping.
How do steroid hormones cause ‘non-dipping’?
We have awarded Jess with an innovation grant to investigate how steroid hormones change blood pressure rhythms so that we can try to reduce the risks in patients who are receiving these drugs. Jess thinks that abnormal steroid hormone levels might affect blood pressure by causing mistiming of the body clocks.
Blood vessels in the kidney are important for regulating blood pressure but we know very little about the rhythms that occur in kidney blood vessels. Jess and her team have recently shown that kidney arteries have clocks and that they change how much they constrict or relax depending on the time of day, which in turn may lead to the changes in blood pressure rhythm.
The team will perform genetic analysis of mouse renal arteries over a 24-hour period to understand which genes show a rhythmic behaviour, which might indicate which genes are responsible for time-of-day differences in blood pressure. They will also study which genes are affected by steroid treatment.
What does this mean for patients?
This work will help Jess and the team to understand which genes are important for controlling blood pressure rhythms and may lead to the development of drugs to fix blood pressure rhythm abnormalities in kidney patients.
"I’m absolutely thrilled with this award,” said Jess. “It will enable my lab to uncover how steroid treatment changes the rhythms of genes in the kidney arteries and figure out how these rhythmic gene changes might cause non-dipping blood pressure. This may lead to finding new or time-optimised therapies that will restore blood pressure rhythms in kidney patients.”
Jess’s research is funded by an Innovation Grant from Kidney Research UK for £39,490
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