Human angiotensin receptor subtypes

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The rapid expansion of our knowledge of angiotensin receptors has been led by the development of subtype-specific angiotensin II receptor antagonists and by the cloning and sequencing of the ATT receptor in angiotensin II. Although some actions of angiotensin II have been attributed to AT2 subtype receptors, the importance of these binding sites remains elusive. Nonpeptide, AT] -selective antagonists, such as losartan, block virtually all of the well-known effects of angiotensin II in mammalian cells. The effects of losartan are now being confirmed by the rapidly developing class of nonpeptide, ATi-selective angiotensin II receptor antagonists. In rodents, subtypes of the ATT receptor have been cloned and designated AT^ and AT^, but they have not been functionally distinguished. Such isoforms have not been identified for human ATi receptors. Importantly, it now appears that the AT2 receptor has been cloned. The angiotensin receptors undergoing intense study are those in fetal tissue, brain, endothelial cells, and fibroblasts. Angiotensin ll-induced growth and cardiovascular hypertrophy are the focus of broad-based research efforts. The clinical relevance of angiotensin II receptor subtypes is unknown, but there is growing evidence that AT^-selective agents are effective inhibitors of the angiotensin system in humans.

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