Using data from mice and humans, a Johns Hopkins Medicine research team has found that a cell surface protein that senses odors and chemicals may be responsible for and explain sex differences in blood pressure in mammals. The unusual link between such protein receptors and sex differences in blood pressure, reported in Science Advances, could lead to a better understanding of long-known blood pressure differences between females and males.

Sex Difference in Blood Pressure

The blood pressure of premenopausal females and female mice is usually 10 points lower than that of males for both diastolic and systolic pressure. Some studies suggest that this difference is caused by sex hormones, but the biological basis for these differences is not entirely clear. Despite the known differences in blood pressure between women and men, most clinical guidelines apply the same thresholds for treatment. A closer look at the basic science basis for gender differences in blood pressure could help physicians look at blood pressure treatment in new ways.

Pluznick is a basic scientist who has found unique roles for so-called olfactory receptors in various organs of the body. The tiny proteins on the surface of cells essentially sniff out odors or other chemicals nearby. The Johns Hopkins team began their studies by looking for the locations in the body where a particular odorant receptor – Olfr558 – is found. Olfr558 is one of three olfactory receptors (out of about 350 total) that have been well conserved throughout evolution in many mammals, including humans and mice. The human version of the receptor is called OR51E1.

Previously, the Johns Hopkins team had found Olfr558 in the kidney, and other studies have localized the receptor in organs other than the cells in the nose responsible for odor detection. For this study, the researchers found the receptor in blood vessel cells in the kidney and in juxtaglomerular granular cells, a type of kidney cell that secretes the hormone renin, which plays a key role in regulating blood pressure.Next, the team, led by Pluznick and research associate Jiaojiao Xu, Ph.D., measured blood pressure in young female and male mice during active and resting periods. Male mice with normal levels of the Olfr558 receptor typically had diastolic and systolic blood pressure 10 points higher than female mice. However, when the researchers examined young female and male mice that were genetically engineered to lack the gene for the Olfr558 receptor, they found that blood pressure increased in female mice, while it decreased in male mice, so that the sex difference in blood pressure disappeared.

New Insights Into Blood Pressure Regulation in Men and Women

Preliminary data from the Johns Hopkins team suggest that blood vessel stiffness and renin hormone levels in the blood are possible reasons for the lack of blood pressure variation in mice lacking the receptor. The research team also analyzed genomic information on human tissue data stored in the UK Biobank, focusing on individuals with a rare variant in the human version of the OR51E1 olfactory receptor. Their analysis showed that women and men under the age of 50 with this variant do not show the typical gender-specific differences in blood pressure.

The research team pointed out that no direct molecular pathway could be identified in their work that would show the link between the olfactory receptor and blood pressure variations. These studies still need to be carried out. In future experiments, Pluznick’s team will attempt to determine the exact cell types that control the link between the receptor and blood pressure and hope that a better understanding of the basic biology of this new connection will lead to insights into blood pressure regulation in both sexes.

Gender-Specific Differences in the Risk of Certain Types of Cardiac Arrhythmia

But male and female hearts also show differences. Research at the University of California has shown that female and male hearts react differently to the stress hormone noradrenaline. The researchers built a novel fluorescence imaging system that allows them to use light to see in real time how a mouse’s heart reacts to hormones and neurotransmitters. The mice were exposed to noradrenaline, also known as norepinephrine. Norepinephrine is both a neurotransmitter and a hormone associated with the body’s “fight or flight” response.

The results show that male and female mouse hearts initially react in the same way after exposure to noradrenaline. However, some areas of the female heart normalize faster than those of the male, leading to differences in the electrical activity of the heart. There are gender differences in the risk of certain types of cardiac arrhythmias. Heart disease is the leading cause of death in both men and women. The study revealed a new factor that may contribute to different susceptibility to arrhythmias in men and women, and could have implications for heart diseases such as arrhythmias and heart failure, as well as how different genders respond to medication.