Many Australians suffer from hypertension or high blood pressure, a leading cause of heart attack, stroke, kidney failure, blindness and pregnancy-related complications in the community. The High Blood Pressure Research Unit (HBPRU) has continued its ongoing basic and clinical research into hypertension. We are studying the development of hypertension caused by adrenal glucocorticoid hormones.

Our studies have revealed an important association between glucocorticoid-induced hypertension and altered nitric oxide production and function. Nitric oxide (NO) is important in maintaining normal blood pressure. Our investigations indicate that glucocorticoids reduce NO production resulting in elevated blood pressure. Studies during 2003 have also revealed an association between glucocorticoid-induced hypertension, reduced NO function and elevated reactive oxygen species (ROS), which act by mopping up NO.

We have investigated several strategies to overcome the apparent imbalance between NO and ROS. Xanthine oxidase is responsible for the conversion of the toxic free radical hydrogen peroxide to water and oxygen. Blocking this enzyme with allopurinol decreased urate production, but did not prevent or reverse hypertension.

Tempol, a synthetic superoxide scavenger which mops up ROS, both reversed and prevented two forms of glucocorticoid hypertension in rats.

Vitamin E is a naturally occurring antioxidant in our diet. Alpha- and gamma-tocopherol are the major dietary constituents of Vitamin E. Neither agent was able to reverse established glucocorticoid hypertension in the rat.

The NAD(P)H oxidases are important sources of reactive oxygen species. Administration of apocynin, a blocker of NAD(P)H oxidase, both prevented and reversed glucocorticoid-induced hypertension.

Glucocorticoids have effects on gene expression. In collaboration with Dr Tim Cole (University of Melbourne), we have been investigating how mice deficient in the receptor for glucocorticoids maintain and control their blood pressure, using implantable blood pressure devices. In collaboration with Dr Frances Shannon (Division of Molecular Bioscience, JCSMR) we have been investigating changes in gene expression in the kidney following glucocorticoid treatment, using micro-array gene technology.

In collaboration with Dr George Mangos and Associate Professor John Kelly (St George Hospital, Sydney) clinical studies were conducted into cortisol-induced hypertension and the effect of synthetic steroids on blood vessel function.

Taken together, our studies suggest an imbalance of NO (deficiency) and ROS (excess) is important in the causation of glucocorticoid hypertension.