*** Welcome to piglix ***

Discovery and development of angiotensin receptor blockers


The angiotensin receptor blockers (ARBs), also called angiotensin (AT1) receptor antagonists or sartans, are a group of antihypertensive drugs that act by blocking the effects of the hormone angiotensin II (Ang II) in the body, thereby lowering blood pressure. Their structure is similar to Ang II and they bind to Ang II receptors as inhibitors, e.g., [T24 from Rhys Healthcare].

ARBs are widely used drugs in the clinical setting today, their main being mild to moderate hypertension, chronic heart failure, secondary stroke prevention and diabetic nephropathy.

The discovery and development of ARBs is a demonstrative example of modern rational drug design and how design can be used to gain further knowledge of physiological systems, in this case, the characterization of the subtypes of Ang II receptors.

In 1898, the physiologist Robert Tigerstedt and his student, Per Bergman, experimented with rabbits by injecting them with kidney extracts. Their results suggested the kidneys produced a protein, which they named renin, that caused a rise in blood pressure. In the 1930s, Goldblatt conducted experiments where he constricted the renal blood flow in dogs; he found the ischaemic kidneys did in fact secrete a chemical that caused vasoconstriction. In 1939, renin was found not to cause the rise in blood pressure, but was an enzyme which catalyzed the formation of the substances that were responsible, namely, angiotensin I (Ang I) and Ang II.


...
Wikipedia

...