Key result
Chronic systemic or intracerebroventricular administration of losartan or aliskiren normalized blood pressure in TGR rats primarily via sympathoinhibition.
Why the study?
Because systemic RAS blockade inhibits brain RAS, the specific effects of central RAS blockade on angiotensin II-dependent versus sympathetic vasoconstriction in hypertensive TGR rats remained unknown.
In a transgenic rat model of hypertension, central sympathoinhibition is the primary mechanism of blood pressure reduction during chronic brain or systemic RAS blockade.
Central RAS blockade may attenuate sympathetic vasoconstriction in hypertensive rats; leaves open any clinical translation from this animal model.
Our previous studies demonstrated that chronic systemic blockade of renin-angiotensin system (RAS) lowered blood pressure (BP) of Ren-2 transgenic rats (TGR) by the attenuation of both angiotensin II-dependent and sympathetic vasoconstriction. Since systemic RAS blockade also inhibits brain RAS, we were interested which effects on these two types of vasoconstriction will have the central RAS blockade in hypertensive TGR rats. Adult male heterozygous TGR rats and their Hannover Sprague Dawley (HanSD) controls were subjected to chronic systemic or intracerebroventricular administration of either angiotensin type 1 receptor blocker losartan or direct renin inhibitor aliskiren for 4 weeks. Additional groups of TGR and HanSD rats were used for the evaluation of acute peripheral and brain effects of angiotensin II. Both chronic systemic and intracerebroventricular administrations of losartan or aliskiren normalized BP of TGR animals. BP effect of brain RAS blockade was based solely on the reduced sympathetic vasoconstriction, while systemic RAS blockade attenuated both angiotensin II-dependent and sympathetic vasoconstriction. Surprisingly, neither peripheral nor central pressor effects of acute angiotensin II administration were enhanced in TGR compared to HanSD rats. In conclusion, sympathoinhibition represents the main mechanism of BP reduction in heterozygous TGR rats subjected to chronic brain or systemic RAS blockade, while peripheral attenuation of angiotensin II-dependent vasoconstriction during systemic RAS blockade is less important. Our data suggest that the participation of angiotensin II in BP control of adult heterozygous TGR rats is shifted from peripheral vasoconstriction to central sympathoexcitation. Similar mechanisms cannot be excluded in human essential hypertension.
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Řezáčová et al. (2019) studied Hypertension. Losartan or aliskiren vs. Hannover Sprague Dawley controls was evaluated on Blood pressure. Chronic systemic or intracerebroventricular administration of losartan or aliskiren normalized blood pressure in TGR rats primarily via sympathoinhibition.
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