Sustained decrease in nitric oxide bioavailability determines female cardiac vulnerability to ischemic challenge

Lead researcher

Dr Morag Young

Main finding

Chronic reduction of nitric oxide bioavailability induced cardiac inflammation and fibrosis equivalently in male and female hearts. Post-acute ex vivo ischemia/reperfusion, female hearts displayed diastolic abnormality, reduced contractile recovery and increased ectopic beats. These functional changes were associated with regulation of genes involved in cardiomyocyte calcium and sodium handling. In addition, cardiomyocyte specific deletion of the mineralocorticoid receptor attenuated the female-specific responses, highlighting the potential for MR involvement in sex-specific ischemic outcomes.


Centre for Endocrinology and Metabolism

Research group

Cardiovascular Endocrinology


Laura A. Bienvenu, James Morgan, Melissa E. Reichelt, Lea M.D Delbridge, Morag J. Young.

Journal and article title

Most surprising

This study provides novel demonstration that sustained in vivo nitric oxide deficiency reduces contractile recovery post-acute ischemia in female, not male, hearts. Thus providing a potential mechanism for ischemic cardiac injury in females in the clinical setting. Our findings provide new evidence demonstrating that new therapeutic strategies aimed at regulation of nitric oxide levels need to consider sex-specific nuances in order to produce beneficial effects.

Future implications

This study shows that a sustained decrease in nitric oxide bioavailability determines female cardiac vulnerability to ischemic injury and raises questions about the role of cardiomyocyte mineralocorticoid receptor mediating these effects. Moreover, these data confirm that further work understanding the sex-specific responses in different disease setting is required. Moving forward it will be important to consider low nitric oxide levels as a complication factor in females with cardiovascular disease and the potential for mineralocorticoid receptor suppression as a useful first or second line therapy.

Disease/health impact

Nitric oxide is an important regulator of cardiac function and out data show that chronic reduction of nitric oxide bioavailability reduces functional recovery in female, but not male, hearts. In addition, loss of cardiomyocyte mineralocorticoid receptor signalling attenuates this sex-specific effect indicating that suppression of mineralocorticoid receptor signalling is protective in a wide range of cardiovascular injuries.