Related Experiment Videos
Emerging concepts in antihypertensive therapy: the benefits of angiotensin II blockade
Insights
Essential hypertension impacts millions, disproportionately affecting African Americans with severe complications. Angiotensin II (ANG II) plays a key role in end-organ damage, suggesting ANG II receptor antagonists as effective treatments.
Area of Science:
- Cardiology
- Nephrology
- Pharmacology
Background:
- Essential hypertension affects a significant portion of the adult population, with higher prevalence and complications in African Americans.
- Hypertensive nephrosclerosis remains a major cause of kidney failure, especially in African Americans.
- The renin-angiotensin system (RAS) is now understood to involve local tissue formation of angiotensin II (ANG II).
Purpose of the Study:
- To review the role of ANG II in end-organ damage associated with essential hypertension.
- To discuss the benefits of ANG II blockade at the end-organ level, independent of blood pressure reduction.
- To highlight the emerging use of ANG II receptor antagonists in treating essential hypertension.
Main Methods:
- Review of current literature on the renin-angiotensin system and its role in hypertension.
- Analysis of the impact of ANG II on cellular processes, vascular remodeling, and organ damage.
- Evaluation of therapeutic strategies targeting the RAS, particularly ANG II receptor antagonists.
Main Results:
- ANG II is implicated in pathological cell growth, cell death, and vascular/myocardial remodeling in hypertension.
- ANG II blockade demonstrates benefits at the end-organ level, potentially separate from its blood pressure-lowering effects.
- Angiotensin-converting-enzyme-independent pathways for ANG II formation offer new therapeutic targets.
Conclusions:
- ANG II is a critical factor in end-organ damage in essential hypertension.
- ANG II receptor antagonists show promise as first-line treatments for essential hypertension.
- Targeting ANG II pathways offers novel strategies for managing hypertensive complications.
Abstract:
Essential hypertension affects more than 40 million Americans, or one in four adults. The prevalence of hypertension is greater among the African-American population, with a distressingly high rate of end-organ complications. Although diabetes mellitus has surpassed hyper tension as the dominant etiology of end-stage renal disease in the United States, kidney failure secondary to hypertensive nephrosclerosis remains a significant problem, particularly among African Americans. During the past decade, a shift in the paradigm for the renin-angiotensin system (RAS) has evolved from a circulating vasoactive cascade toward angiotensin II (ANG II) formation at the cellular level. The molecular components of the RAS have been identified in cells, documenting the existence of an autocrine tissue RAS, as well as the presence of enzymes, which catalyze the formation of ANG II by angiotensin-converting-enzyme-independent pathways, providing new targets for therapeutic intervention. The latter challenge has important clinical implications, in view of recent evidence implicating ANG II in pathologic cell growth and cell death and fundamental events in the remodeling of the vascular wall and myocardium in the setting of hypertension. This review focuses on ANG II as a major determinant of end-organ damage in essential hypertension; the benefits of ANG II blockade at the end-organ level, which appear to be independent of the blood pressure-lowering effect; and the emerging role for ANG II receptor antagonists as first-line agents in the treatment of essential hypertension.