A new study published in Science advances It shows that female and male hearts respond differently to the stress hormone noradrenaline. The study in mice may have implications for human heart disorders such as arrhythmias and heart failure and how different races respond to medication.
The team built a new type of fluorescence imaging system that allows them to use light to see how the mouse heart responds to hormones and neurotransmitters in real time. Mice were exposed to norepinephrine, also known as norepinephrine. Noradrenaline is a neurotransmitter and hormone associated with the body’s “fight or flight” response.
The results show that the hearts of male and female mice respond uniformly initially after exposure to norepinephrine. However, some areas of the female heart return to normal more quickly than the male heart, which results in differences in the electrical activity of the heart.
“The differences in electrical activity that we observed are called repolarization in female hearts,” said Jessica L. Caldwell, first author of the study. “Repolarization indicates how the heart resets between each heartbeat and is closely associated with some types of arrhythmias.” Caldwell is a postdoctoral scientist in the department of pharmacology at the University of California, Davis School of Medicine.
“We know that there are gender differences in the risk of developing certain types of arrhythmias,” Caldwell said. “The study reveals a new factor that may contribute to the different susceptibility to arrhythmias between men and women.”
Heart disease is the leading cause of death in the United States
Heart disease is the leading cause of death for both men and women in the United States. It accounts for about 1 in 4 male deaths 1 1 in 5 deaths are female in 2020. Despite affecting both sexes, heart disease research has largely been done on males.
In this study, the researchers were interested in looking at factors that may contribute to arrhythmias. An arrhythmia is a type of heart disorder in which the electrical impulses that control heartbeat do not work properly. It affects somewhere between 1.5% to 5% of the population.
The new imaging system uses a mouse, called a CAMPER mouse, that has been genetically modified to emit light during a very specific chemical reaction in the heart – cAMP binding.
The cAMP molecule (short for cyclic adenosine 3′,5;-monophosphate) is an intermediate messenger that converts signals from hormones and neurotransmitters, including noradrenaline, into action from heart cells.
Optical signals are transmitted from the CAMPER mouse by a biosensor that uses fluorescence resonance energy transfer (FRET). This FRET signal can be captured at high speed and at high resolution by a new imaging system specifically designed for hearts. This allows the researchers to record the heart’s reaction to noradrenaline in real time, along with changes in electrical activity.
This new imaging approach revealed differences in cAMP breakdown in female and male mice and related differences in electrical activity.
Including a female rat leads to discoveries
The researchers did not plan to study responses based on gender, according to Crystal M. Ripplinger, senior author of the study. But the researchers began to see a pattern of different reactions, which led them to realize that the differences were based on gender.
Ripplinger is an electrical and biomedical engineer and professor in the department of pharmacology.
When she started her lab at the University of California, Davis School of Medicine more than a decade ago, she used only male animals. This was the norm for most research at the time. But several years ago, she began including both male and female animals in her studies.
“Sometimes the data between the sexes is the same. But if the data starts to show disparity, the first thing we do is look at the differences between the sexes. Using male and female mice has revealed evidence of differences that we never suspected. Researchers are aware that there is no You can extrapolate both sexes from studying just one of them.”
She points out that from the current study, it is not clear what the differences in cAMP and electrical activity might mean.
“The response of female mice may or may not be protective. But simply documenting an appreciable difference in response to the stress hormone is important. We hope to learn more in future studies,” Replinger said.
Additional authors on the study include Ai Gu (Eric) Lee, Lina Ngo, Lianguo Wang, Donald M. Pierce, Manuel F. Navido, and Julie Bossuyt of the University of California, Davis. Sherif Bahreez of the University of California Davis and Mansoura University. Bing (Rita) Xu and Yang K. Xiang of UC Davis and VA Northern California.
This work was supported by grants from the National Institutes of Health, the American Heart Association, and a Veterans Administration benefit grant.