What Are Renin Inhibitors?

Renin inhibitors are a class of drugs used to treat high blood pressure, or hypertension, by inhibiting an enzyme called renin. These medications form one of the pharmaceutical categories used for regulating the activity of the renin-angiotensin system (RAS), which is best known for controlling blood pressure but also controls fluid volume. In this hormone system, renin is the enzyme that determines these vital signs. Renin inhibitors are also known as renin blockers, renin antagonists or inhibitors of renin.

When low blood pressure, or hypotension, occurs in the body, the renin-angiotensin system becomes active. Renin is then released from the juxtaglomerular cells of the kidney. It reacts with a serum protein called angiotensinogen, which is released by the liver into the blood plasma. This reaction, which involves the renin cleaving the angiotensinogen, produces angiotensin I.

Angiotensin I is the inactive form of the angiotensin peptide, so another reaction is needed to make it active. This occurs when the angiotensin I-converting enzyme (ACE), which originates in the lungs’ capillaries, eliminates two C-terminal residues of angiotensin I, and it is converted to angiotensin II. The high blood pressure occurs when angiotensin II constricts, or narrows, the blood vessels. It also contributes to retention of sodium and water in the kidney, thus damaging them.

Although different types of pharmaceuticals have been developed to combat hypertension as a result of the renin-angiotensin system’s high level of activity, renin inhibitors in particular were not developed until the end of the 20th century. Renin’s contribution to high blood pressure had been discovered a century earlier, but since then, the drugs that were developed, ACE inhibitors and angiotensin II receptor blockers (ARBs), focused on the transformation of angiotensin I to angiotensin II and the inhibition of the latter, respectively. The idea of renin inhibitors was generated when it was discovered that some patients were not reacting favorably to ACE inhibitors or ARBs but did experience an increase in the production of renin.

Perhaps the most popular of renin inhibitors is aliskiren, which goes by the trade name Tekturna in the United States, and Rasilez in other countries. The U.S. Food and Drug Administration (FDA) approved it for treatment of hypertension in 2007. Other renin inhibitors include remikiren, which preceded aliskiren by a decade and is manufactured by Swiss healthcare corporation Hoffmann-Roche; and enalkiren, which is more obscure than the aforementioned pharmaceuticals.