Previous research has shown that high dietary salt intake and obesity, when combined, deliver more damage to the heart and kidneys than the sum of their individual contributions.
Now, Japanese researchers have discovered the molecular mechanisms behind this lethal synergy.
Lead researcher Toshiro Fujita, MD, professor and chairman of the Department of Internal Medicine and chief of the Department of Nephrology and Endocrinology at the University of Tokyo, and colleagues suggest that high dietary salt intake and obesity work together to trigger an abnormal activation of a cellular protein called Rac1.
The team studied the effects of a high-salt diet in rats bred to have high blood pressure and different levels of blood pressure sensitivity to salt.
When obese "salt-sensitive" rats were fed a high-salt diet, the team found that Rac1 activated the mineralocorticoid receptor (MR) on the rats' kidney cells.
This receptor is normally activated by the hormone aldosterone.
When turned on, MR leads to the expression of a protein called epithelial sodium channel (ENaC) and an enzyme called the sodium pump. Both of these substances promote the re-absorption of salt, which causes the body to retain fluid and results in high blood pressure.
This is the first time scientists have seen Rac1 usurp aldosterone's role in activating MR in the regulation of blood pressure.
When Rac1 inhibitors were successful in lowering the rats' blood pressure, the team knew they had discovered a mechanism by which obesity and a high-salt diet team up to wreak havoc on blood pressure and the kidneys.
According to Dr. Fujita, the team's findings carry important implications for the treatment of hypertension.