Over the past decade, angiotensin II receptor antagonists have gradually been cutting into the market previously occupied by ACE inhibitors. Consequently, this is the only class of anti-hypertensive compounds demonstrating significant growth. Current global sales are around $2 million and continue to increase by about 35% per year (based on sales figures from 1998-2001). Since the end of 2000, clinical trial data have been released suggesting that the angiotensin II receptor antagonists may have potential in a number of areas in addition to that of hypertension. For example, in a recent DiscoveryDossier, we describe the potential that angiotensin receptor ligands may play in the treatment of Alzheimer's disease, anxiety and depression.

Chronic hypertension is a major risk factor associated with stroke and hence the use of ACE inhibitors or angiotensin receptor antagonists to control hypertension may be a useful therapeutic approach to the prevention of stroke. In addition to the ability of the renin-angiotensin system to maintain blood pressure by vasoconstriction and stimulation of aldosterone secretion, a role in vascular remodeling during chronic hypertension is now accepted. Researchers at the University of Iowa have most recently investigated this concept. Specifically, the pressure, diameter, and cross-sectional area of the vessel wall in maximally dilated cerebral arterioles was measured in transgenic mice that overexpress both human renin and human angiotensinogen and in spontaneously hypertensive mice, a model of chronic hypertension that is thought to develop independently of the renin-angiotensin system. Systemic arterial pressure under conscious conditions, arteriolar distensibility, and cross-sectional area of the vessel wall were each increased by similar amounts in the two strains of mice. In contrast however, the external diameter of maximally dilated cerebral arterioles was reduced in transgenically hypertensive mice, but not in spontaneously hypertensive mice. Thus, cerebral arterioles undergo remodeling and hypertrophy in transgenically hypertensive mice, but only hypertrophy in spontaneously hypertensive mice. These findings support the hypothesis that the renin-angiotensin system is an important determinant of vascular remodeling during chronic hypertension.

Entry date March, 2003

Adapted from Baumbach et al, Hypertension 2003 Jan;41(1):50-5 - Interested in collaborating with this group? Contact LeadDiscovery or the authors direct.

Interested in collaborating with this group? Contact leaddiscovery@bioportfolio.co.uk