A recent study has uncovered how the hearts of males and females respond differently to the stress hormone noradrenaline.
The team of researchers, led by the UC Davis School of Medicine, used a new type of fluorescence imaging system that allowed them to see how a mouse heart responds to hormones and neurotransmitters in real-time.
Published in Science Advances, the results of the study in mice may have implications for human heart disorders like arrhythmias and heart failure and how different sexes respond to medication.
The study found that when exposed to noradrenaline, both male and female mouse hearts responded uniformly at first. However, the researchers observed that some areas of the female heart returned to normal more quickly than the male heart, which produced differences in the heart’s electrical activity. This difference in electrical activity is known as repolarization, which is closely linked to certain types of arrhythmias.
Heart disease is a leading cause of death for both men and women in the United States, accounting for about 1 in every 4 male deaths and 1 in every 5 female deaths in 2020. Despite the impact on both sexes, cardiology research has largely been performed on male subjects. This new study brings attention to the importance of including both sexes in medical research and understanding the potential sex-based differences in response to medication.
The novel imaging system used in the study employed a mouse, called the CAMPER mouse, that had been genetically modified to emit light during a specific chemical reaction in the heart, cAMP binding. The cAMP molecule is an intermediate messenger that turns signals from hormones and neurotransmitters into action from heart cells. The light signals from the CAMPER mouse were transmitted by a biosensor that used fluorescence resonance energy transfer (FRET), allowing the researchers to record the heart’s reaction to noradrenaline in real-time, along with changes in electrical activity.
The senior author of the study, Crystal M. Ripplinger, said that while the researchers had not planned to study sex-based responses, they started seeing a pattern of different reactions, which led them to realize the differences were sex-based. Ripplinger, an electrical and biomedical engineer and a professor in the Department of Pharmacology, noted that when she started her lab at the UC Davis School of Medicine over a decade ago, she exclusively used male animals, which was the norm for most research at the time.
However, several years ago, she began including both male and female animals in her studies, leading to new discoveries and a better understanding of sex-based differences in response to medication.