Angiotensin II receptors and drug discovery in cardiovascular disease

• Published in: Drug discovery today Vol. 16; no. 1; pp. 22 - 34
• Main Authors: Dasgupta, Chiranjib, Zhang, Lubo
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.01.2011; Elsevier
• Subjects: Angiotensin II - metabolism; Angiotensin Receptor Antagonists - chemistry; Angiotensin Receptor Antagonists - pharmacology; Animals; Biological and medical sciences; Cardiovascular Agents - pharmacology; Cardiovascular Diseases - drug therapy; Cardiovascular Diseases - genetics; Cardiovascular Diseases - metabolism; Drug Discovery - methods; Female; General pharmacology; Humans; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Pregnancy; Receptors, Angiotensin - biosynthesis; Receptors, Angiotensin - genetics; Receptors, Angiotensin - metabolism; Drug; Cardiovascular disease; Angiotensin II receptor; Pharmaceutical technology; Research and development
• ISSN: 1359-6446; 1878-5832
• DOI: 10.1016/j.drudis.2010.11.016

Hypertension is one of the cardiovascular diseases that might cause cardiovascular remodeling and endothelial dysfunction besides high blood pressure. Angiotensin II (Ang II) receptors are implicated in hypertension. Genetic and epigenetic manipulations of the Ang II receptors play a crucial part in the programming of cardiovascular diseases, and certain variants of the Ang II type 1 and Ang II type 2 receptors are constitutively predisposed to higher cardiovascular risk and hypertension. In this review, we focus on the expression, mode of action of Ang II receptors, and their role in programming the cardiovascular diseases in utero. In addition, we discuss possible therapeutic interventions of Ang II stimulation. Collectively, this information might lead us to new drug designs against cardiovascular diseases. Intervention of RAS is currently done by ACE-I and ARBs. Identification of additional targets and mode of action of RAS presents new areas for future drug development.