Continuous inhibition of the renin-angiotensin system and protection from hypertensive end-organ damage by brief treatment with angiotensin II type 1 receptor blocker in stroke-prone spontaneously hypertensive rats.

To investigate the short-term blockade of angiotensin II type 1 (AT1) receptor at the prehypertensive stage and its effects on hypertensive sequelae after maturation, we administered AT1 receptor blocker (ARB, 1 mg/kg/day) to male stroke-prone spontaneously hypertensive rats (SHRSP) from 5 to 10 weeks of age. Although blood pressure in the treated group was significantly lower than in the control group at 10 weeks of age, it gradually increased within 2-3 weeks and reached approximately 250 mm Hg at 17 weeks after cessation of the treatment (27 weeks of age), and reached parity with the control after 20 weeks of age. Nonetheless, hypertensive end-organ damage such as cerebral lesion, cardiac hypertrophy and nephrosclerosis were markedly suppressed in the treated group. Plasma renin activity (PRA), plasma angiotensin II (AII) levels and cerebral angiotensin-converting enzyme (ACE) activity were also significantly lower in the treated group than in the control group, indicating continuous suppression of the circulating and local renin-angiotensin system (RAS). In the brain, intercellular adhesion molecule-1 (ICAM-1) mRNA expression was significantly lower in the cerebral cortex of the treated group than in the control group, while AT1 receptor expression was similar. Such beneficial effects by ARB treatment were not found in the hydralazine-treated group, even though blood pressure changes were similar in both groups. These results demonstrated that early and transient treatment by ARB effective for the prevention of hypertensive end-organ damage. This may be due to the low concentration of plasma angiotensin II by continuous inhibition of RAS even after maturation.