Roxanne Fernandes, Hannah Garver, Jack R. Harkema, James J. Galligan, Gregory D. Fink, Hui Xu (Hypertension, 2018)
High fat diets (HFD) are known to lead to obesity, hypertension, and renal dysfunction. A HFD can also lead to an increase in sympathetic outflow, which is the main cause of hypertension. Hypertension is chronically high blood pressure and is one of the major causes of renal disease. Although sex differences in obesity and cardiovascular disease have been researched, it is not known how a HFD causing hypertension and renal injury differ between males and females. The goal of this study is to see if there are differences in blood pressure, renal injury, and fat accumulation between sexes.
This study used HFD Dahl SS rats that exhibit signs of HFD-induced hypertension and Sprague Dawley rats that are also fed HFD but are not hypertensive. Beginning at three weeks old, the rats were either given a control diet that had normal salt levels or a HFD. The Dahl SS rats were given the HFD for either 10, 17, or 24 weeks, while the Sprague Dawley rats were placed on the HFD for 24 weeks.
After 24 weeks HFD males and females exhibited an increase in adipose tissue and body weight than the control rats. Body weights remained similar in all groups through week 8 of the diet, but then the control and the HFD males body weight increased significantly more than the females. Leptin, which is produced by adipose cells, was also shown to increase in males and females that were fed the HFD. Rats given the HFD also exhibited increased blood pressure. After 10 weeks of the diets, there was no significant difference between HFD and control rats. At 15 weeks the blood pressure of HFD rats became significantly higher than the controls rats. From 15 weeks to 24 weeks blood pressure in the HFD rats continued to significantly increase compared to the control rats. The heart rates between the HFD and control rats did not differ throughout the 24 week experiment.
At 24 weeks, rats were given an injection of hexamethonium, which is a ganglionic blocker for sympathetic nerve activity. The hex injection decreased blood pressure more in the HFD males than the control males. The female rats exhibited a larger blood pressure decrease in the control rats than the HFD rats. When comparing males and females, the HFD males exhibited a larger blood pressure decrease compared to the HFD females.
Researchers also observed renal histological changes. At 10 weeks, male rats had higher renal injury scores than females in both the HFD and control groups. At 17 weeks, male rats given the HDF exhibited significantly higher renal injury scores than the HFD females or the control groups. At 24 weeks, the HFD males exhibited an increased injury score compared to 17 weeks. This time period was also when blood pressure in HFD males and females was significantly increased.
Researchers then looked at the renal inflammatory responses in HFD rats. At 10 weeks, cortical and medullary macrophage infiltration was higher in males than females. At 17 weeks, macrophage levels increased in females of both diets, while males stayed similar to 10 week males. At 24 weeks, female rats exhibited a decrease in macrophages when compared to 17 week females, but still higher than 10 week females. While macrophage levels in males at 24 weeks was similar to the males at 10 and 17 weeks, levels were overall higher than female macrophage levels. The levels of cortical and medullary T-cells were then measured. At 10 weeks, all male and females had lower levels of T-cells. T-cells increased at 17 weeks through 24 weeks in males but not females, which exhibited similar T-cells levels to 17 weeks. Levels of inflammatory cytokines did not exhibit a significant change between different diets.
In conclusion, the HFD males and females both exhibited an increase in adipose tissue compared to the controls, but males generally have a higher body weight. Male and female rats given the HFD exhibited increase blood pressure, while heart rate shoed no significant difference between groups. The ganglionic blocker hexamethonium lead to a larger decrease in blood pressure in male rats compared to female rats with HFDs. Renal injury increased over the course of 24 weeks in males, while renal injury in females remained lower over the 24 week experiment. Renal T-cell levels increased over 24 in both HFD and control male rats, while females did not.
One of the major limitations of this study that researchers discussed is how sex hormones effect hypertension and organ damage. They discuss that future studies could observe how sex hormones and receptors play a role in sex differences in hypertension. Another limitation discussed by researchers was how the HFD caused fat accumulation. Future studies could show that other high calorie diets can dramatically change renal inflammation or hypertension. I chose this paper because Dr. Fink recently spoke to the department and although his research is different than what we are doing in lab, it is also very closely related. Dr. Fink’s lab is mostly focusing on the sedentary side of our research and is now beginning to look towards how sex hormones are affecting hypertension.
-Paul M.
No comments:
Post a Comment