Pressor Responses to Central Sodium and Ouabain Are Attenuated in Transgenic Rats Deficient in Brain Angiotensinogen

Abstract

P195 Studies using AT 1 -blockers suggest that the brain renin-angiotensin system (RAS) contributes to sympatho-excitation and hypertension by high dietary salt or central sodium loading. To more specifically examine this role of the brain RAS, [TGR (AsrAOGEN)] transgenic rats were used. These rats express an antisense RNA against angiotensinogen mRNA specifically in the brain, and the brain angiotensinogen level is reduced by more than 90%. In freely moving TGR and SD controls, BP and HR responses to intracerebroventricular (icv) infusion (3.8 μl/min for 10 min) of artificial CSF (aCSF) and Na + -rich aCSF (containing 0.2, 0.3 and 0.45 M Na + ) as well as icv injection of ouabain (0.3 and 0.6 μg/2 μl) were assessed. The vasopressin antagonist [d(CH 2 ) 5 Tyr(Me)]AVP (30 μg/kg) was given iv before each icv infusion. Data are means±SEM (n=6, for each).* p + -rich aCSF support the concept that the brain RAS plays an important role in the sympatho-excitatory effects of ouabain and CSF sodium.