Researcher says high blood pressure is not only about the renin-angiotensin-aldosterone system.
Hypertension researchers and clinicians traditionally focus on suppressing the renin-angiotensin-aldosterone system that prompts the body to retain salt and thereby raises blood pressure. However, they shouldn’t ignore the powerful endothelin system, which helps the body eliminate salt, says Dr. David Pollock, Chief of the Section of Experimental Medicine at the Medical College of Georgia at Georgia Regents University.
Pollock explains that the first system is important as a protective mechanism that makes sure the body has enough sodium to keep blood pressure at sufficient levels to sustain life. When blood volume is low the kidneys secrete renin to make the hormone angiotensin. Angiotensin in turn drives blood pressure up by promoting sodium retention and by stimulating the release of aldosterone, a hormone that prompts the kidneys to reabsorb sodium rather than eliminate it in the urine.
However, Pollock gives three reasons why enhancing sodium excretion through the endothelin system might be a better approach. Firstly, most Americans already turn down the renin-angiotensin-aldosterone system by eating too much salt. Secondly, and the system is “somehow dysregulated in some hypertensive patients who take ACE inhibitors or angiotensin receptor blockers to turn it down.” Thirdly, enhancing sodium excretion is particularly relevant for patients not responding to existing therapies that suppress the renin-angiotensin-aldosterone system.
To support his argument, Pollock says that when an animal on a high-salt diet is given a drug to block endothelin’s B receptor, blood pressure goes up 50 points and blocking angiotensin receptors won’t produce nearly such dramatic results. He believes that “problems with the endothelin system – possibly resulting from a developmental defect or high-salt exposure early in life – may help explain why some folks who eat a high-sodium diet get high blood pressure and others don’t. But this leads to one of the weak points of endothelin and probably part of the reason it’s not been top of mind for hypertension researchers,” he said.
Endothelin was labeled the most potent vasoconstrictor ever described when it was first purified in the late 1980s. Pollock’s studies have shown that the kidney’s endothelin B receptor plays a critical role in eliminating both acute and chronic salt loads by activating nitric oxide, a potent dilator of blood vessels, in the kidneys. The kidneys make more endothelin than any place in the body.