©2016 by UVa Health System. Division of Endocrinology.

Basic Overview:

What is a Gene and Allele?

SALT

SENSITIVITY

MECHANISMS

The Dopaminergic System

The kidneys make their own dopamine from a precursor in the body. Dopamine signals cells in the kidney when there is too much sodium in the blood. The signal they send by binding to the D1 receptor tells certain machinery to make more sodium exit the body. The machinery is made of certain transporters NH3 exchanger, NaHCO3 cotransporter, and NaKATPase that are told to move less sodium back into the blood and to excrete more.

The Renin-Angiotensin-Aldosterone System

 

The renin angiotensin aldosterone system is the main hormonal system controlling blood pressure.

To start this system’s pathway, the liver produces angiotensinogen, which binds to the hormone and peptidase renin. Renin comes from the kidneys and splits angiotensinogen to form angiotensin I.  Next, angiotensin converting enzyme (ACE) splits angiotensin I to produce angiotensin II. Angiotensin II travels through the adrenal glands and stimulates aldosterone production.

Salt sensitivity is a measure of how your blood pressure responds to salt intake. People are either salt-sensitive or salt-resistant. Those who are sensitive to salt are more likely to have high blood pressure than those who are resistant to salt. There is also a less common phenomena referred to as inverse salt sensitivity, in which a person’s salt intake results in a lower blood pressure.

Basic Overview:

The RAS and Blood Pressure 

Our study looks at a gene called GRK4. This gene codes for a protein product which is also called GRK4. This protein is important because its interactions with the D1 receptor can cause the receptor to become inactivated. This means dopamine can’t tell the cell to stop putting sodium back into the blood, leading to an increase in blood pressure.

Based on our previous research, we believe that people with certain genetic variants that make a GRK4 protein that deactivates the D1 receptor are more susceptible to changes in blood pressure when they take in more sodium.

Aldosterone works in the distal convoluted tubule and collecting tubule to reabsorb sodium back into the body and excrete potassium into the urine. Angiotensin II also causes vasoconstriction, or shrinking of the arterioles that carry blood through the body. The two actions of angiotensin II  - vasoconstriction and secretion of aldosterone - are mediated by the receptor AT1. There is also an AT2 receptor to which angiotensin II binds. The AT2 receptor has the opposite effect of the AT1 receptor; it promotes salt excretion and vasodilation.