Treating hypertension – a new approach

Hypertension is the leading cause of cardiovascular disease, affecting 1.13 billion people worldwide, including six million adult Australians.

Research has indicated that a new pharmacological approach to treatment could be imminent,¹ following the results of a recent study in mice.²

Despite the prevalence and mortality rate attributed to hypertension, effective treatment remains challenging, according to Professor Grant Drummond, Co-director of La Trobe University’s Research Centre for Cardiovascular Biology and Disease.

‘Up to 20% of patients with high blood pressure fail to have their condition controlled by current therapies – which include diuretics, blood vessel dilating agents and drugs that reduce heart rate,’ he said.

Professor Drummond and his research team – comprised of collaborators from La Trobe University, Baker University, Hudson Institute and University of Bonn in Germany – are leading a major research project into treating renal inflammation.

Renal inflammation, leading to fibrosis and impaired function, is a major contributor to the development of hypertension. NLRP3 is an inflammatory enzyme found in the kidneys.³

‘Once activated, this enzyme produces chemical signals that attract immune cells, setting up an inflammatory response that disrupts the blood pressure-regulating functions of the kidneys and blood vessels,’ Dr Samuel Vinh, one of the lead authors on the study, said.

‘This process is normally used to protect us from bacteria and viruses, but occasionally immune cells get confused and mount a response to relatively harmless substances.

‘In the case of hypertension, the “harmless” substances that appear to be at the centre of the problem are glass-like shards of crystalline salt, cholesterol and uric acid that build up in the blood vessels and kidneys.’

Dr Drummond and his team observed that MCC950, a drug recently found to be an inhibitor of NLRP3, limits renal inflammation, fibrosis and dysfunction in mice with established hypertension.³

While the research is still in its early stages, Professor Drummond and his team are optimistic about its impact.

‘Inflammation-suppressing drugs are already used for the treatment of autoimmune diseases such as rheumatoid arthritis and gout… We have [now] shown that similar drugs can be used just as effectively to reduce blood pressure in mice with hypertension,’ Professor Drummond said.

‘These findings could pave the way for new treatment approaches, where drugs currently reserved for patients with autoimmune diseases are repurposed for the treatment of high blood pressure.’

‘Ultimately this could help save millions of lives and significantly reduce the global burden of disease resulting from high blood pressure,’ he said.

References

1. World Health Organisation. Global Health Observatory (GHO) data. At: https://www.who.int/gho/ncd/risk_factors/blood_pressure_prevalence/en/
2. Australian Heart Foundation. Heart Disease in Australia. At: https://www.heartfoundation.org.au/about-us/what-we-do/heart-disease-in-australia
3. Krishnan SM, Ling YH, Huuskes BM, Ferens DM, Saini N, Chan CT, Diep H, Kett MM, Samuel CS, Kemp-Harper BK, Robertson AAB, Cooper MA, Peter K, Latz E, Mansell AS, Sobey CG, Drummond GR, Vinh A. Pharmacological inhibition of the NLRP3 inflammasome reduces blood pressure, renal damage, and dysfunction in salt-sensitive hypertension. Oxford Academic: Cardiovascular Research 2018. At: https://academic.oup.com/cardiovascres/advance-article/doi/10.1093/cvr/cvy252/5144200