Systolic hypertension is a major risk factor for
cardiovascular disease. The determinants of systolic blood pressure are peripheral resistance and arterial compliance. Arterial vasoconstriction, vascular growth and fluid retention, induced by the renin-angiotensin system directly or indirectly by enhancing sympathetic nervous system activity, are important factors in increasing peripheral resistance, decreasing arterial compliance and, consequently, elevating systolic blood pressure. Selective blockade of the
angiotensin II type 1 (AT1) receptor represents a novel mechanism for interrupting the renin-angiotensin system. This provides the additional benefit of blocking
angiotensin II generated by non-
angiotensin-converting-enzyme pathways without altering either
bradykinin metabolism or the potential beneficial effects of AT2 receptor stimulation.
Eprosartan is a potent (1.4 nmol/l) AT1 receptor antagonist that inhibits
angiotensin-II-induced vascular contraction in a competitive manner.
Eprosartan is effective in reducing
disease progression in animal models of
hypertension,
heart failure, renal disease and
stroke. Furthermore,
eprosartan causes a large increase in arterial compliance in hypertensive rats fed high-
salt and high-fat diets.
Eprosartan also possesses sympathoinhibitory activity as demonstrated by an inhibition of the pressor responses induced by activation of sympathetic outflow through
spinal cord stimulation in pithed rats. In contrast, other
angiotensin II receptor antagonists, such as
losartan, used at equivalent
angiotensin II blocking activity, do not appear to alter sympathetic nervous system activity.
Angiotensin II receptor antagonists, such as
eprosartan, that have the ability to block both the direct effects of
angiotensin II and the indirect effects mediated by enhanced sympathetic neurotransmission, may represent an important advance in the treatment of elevated systolic blood pressure.