LAUSR

Objectives: Chronic blockade of renin-angiotensin system (RAS) lowered blood pressure (BP) in Ren-2 transgenic rats (TGR) by attenuation of both angiotensin II-dependent and sympathetic vasoconstriction. The aim of our study was to determine whether central RAS blockade has different effects on principal vasoactive systems contributing to BP maintenance in hypertensive TGR rats than systemic RAS blockade. Methods: Adult male heterozygous TGR rats and their HanSD controls were used for evaluation of acute systemic and central effects of angiotensin II. Furthermore, TGR rats were treated with AT1 receptor blocker losartan or direct renin inhibitor aliskiren administered either systemically or intracerebroventricularly (icv) for 4 weeks. Results: BP effects of systemic or icv angiotensin II administration were similar in both strains. Chronic systemic or central administration of losartan or aliskiren normalized BP of TGR animals. Systemic RAS blockade attenuated both angiotensin II-dependent and sympathetic vasoconstriction, while BP effect of central RAS blockade was based solely on reduced sympathetic vasoconstriction. Conclusion: Neither peripheral nor central pressor effects of angiotensin II are enhanced in TGR compared to HanSD rats. Sympathoinhibition is involved in BP decrease induced by chronic RAS inhibition in TGR rats, being the main mechanism of BP reduction in rats subjected to central RAS blockade. Supported by grant AZV 15-25396A (Ministry of Health of the Czech Republic)