PS 04-16 THE EFFECTS OF CENTRAL VERSUS PERIPHERAL RAS BLOCKADE ON MAJOR VASOACTIVE SYSTEMS CONTRIBUTING TO BLOOD PRESSURE MAINTENANCE IN ADULT REN-2 TRANSGENIC RATS

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Abstract

Objective:

In young Ren-2 transgenic rats (TGR), we have recently demonstrated that chronic peripheral blockade of renin-angiotensin system (RAS) with different types of RAS blockers lowered blood pressure by the similar mechanism, i.e. by the attenuation of both RAS- and sympathetic-dependent vasoconstriction. We were interested whether the central blockade of renin-angiotensin system would have other effects on principal vasoactive systems contributing to blood pressure (BP) maintenance in adult TGR rats than peripheral blockade.

Design and Method:

Adult (4-month-old) male heterozygous TGR rats were given angiotensin receptor blocker losartan in drinking fluid (10 mg/kg/day) or direct renin inhibitor aliskiren via osmotic minipumps into peritoneal cavity (10 mg/kg/day). These drugs were also administered intracerebroventricularly using osmotic minipumps (aliskiren and losartan - 2 mg/kg/day) for 4 weeks. At the end of the study basal BP and acute BP responses to consecutive blockade of renin-angiotensin (RAS), sympathetic nervous (SNS), and nitric oxide (NO) systems were determined in conscious rats.

Results:

Both peripheral and central RAS blockade normalized BP. Peripheral RAS blockade attenuated both RAS- and SNS-dependent vasoconstriction while the effect of central RAS blockade was mediated only by the reduction of sympathetic vasoconstriction. In addition, central RAS blockade moderately reduced NO-dependent vasodilation.

Conclusions:

Contrary to peripheral RAS blockade the central inhibition of RAS system is fully dependent on sympathoinhibition.

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