Abstract
Effective blood pressure control with a large arsenal of conventional antihypertensive drugs, such as diuretics, beta-adrenergic blockers, and calcium channel blockers, significantly reduce the morbidity and mortality associated with cardiovascular disease. However, blood pressure control with these drugs does not reduce cardiovascular disease risks to the levels in normotensive persons. Only two drug classes that inhibit or antagonize portions of the renin-angiotensin system (RAS), angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor type-1 (AT1 receptor) blockers, have protective and beneficial effects unrelated to the degree of blood pressure reduction. These drugs may prevent the blood pressure related functional and structural abnormalities of the cardiovascular system and reduce the end organdamage. The first part of this review presents the components of the RAS, biological actions of angiotensin peptides, and the functions of the enzymes that generate and metabolize angiotensins, including the likely effect of manipulating them. Special attention is devoted to renin, ACE, ACE2, chymase, and neprilysin. The second part of this review presents the rationale for targeting the RAS, based on clinical studies of the ACE inhibitors and AT1 receptor blockers. Finally, we present the investigational agents acting on the RAS that have a potential for clinical usage, and give the perspective of pharmacological, immunological and gene targeting of the RAS for treatment of cardiovascular disease.
Keywords: renin-angiotensin system, Angiotensinogen, Chymase, Vasopeptidase Inhibitors, Renin Inhibitors
Current Pharmaceutical Design
Title: Pharmacological, Immunological, and Gene Targeting of the Renin-Angiotensin System for Treatment of Cardiovascular Disease
Volume: 13 Issue: 12
Author(s): Rajko Igic and Rahim Behnia
Affiliation:
Keywords: renin-angiotensin system, Angiotensinogen, Chymase, Vasopeptidase Inhibitors, Renin Inhibitors
Abstract: Effective blood pressure control with a large arsenal of conventional antihypertensive drugs, such as diuretics, beta-adrenergic blockers, and calcium channel blockers, significantly reduce the morbidity and mortality associated with cardiovascular disease. However, blood pressure control with these drugs does not reduce cardiovascular disease risks to the levels in normotensive persons. Only two drug classes that inhibit or antagonize portions of the renin-angiotensin system (RAS), angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor type-1 (AT1 receptor) blockers, have protective and beneficial effects unrelated to the degree of blood pressure reduction. These drugs may prevent the blood pressure related functional and structural abnormalities of the cardiovascular system and reduce the end organdamage. The first part of this review presents the components of the RAS, biological actions of angiotensin peptides, and the functions of the enzymes that generate and metabolize angiotensins, including the likely effect of manipulating them. Special attention is devoted to renin, ACE, ACE2, chymase, and neprilysin. The second part of this review presents the rationale for targeting the RAS, based on clinical studies of the ACE inhibitors and AT1 receptor blockers. Finally, we present the investigational agents acting on the RAS that have a potential for clinical usage, and give the perspective of pharmacological, immunological and gene targeting of the RAS for treatment of cardiovascular disease.
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Cite this article as:
Igic Rajko and Behnia Rahim, Pharmacological, Immunological, and Gene Targeting of the Renin-Angiotensin System for Treatment of Cardiovascular Disease, Current Pharmaceutical Design 2007; 13 (12) . https://dx.doi.org/10.2174/138161207780618876
DOI https://dx.doi.org/10.2174/138161207780618876 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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