Pressor Responses to Central Sodium and Ouabain Are Attenuated in Transgenic Rats Deficient in Brain Angiotensinogen
Studies using AT1-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(CH2)5Tyr(Me)]AVP (30 μg/kg) was given iv before each icv infusion. Data are means±SEM (n=6, for each).* p<0.05, vs SD rats. Somewhat surprisingly, angiotensin I and II levels of not only hypothalamus but also plasma were lower in TGR vs. SD rats. The clearly attenuated sympatho-excitatory and pressor effects to ouabain and Na+-rich aCSF support the concept that the brain RAS plays an important role in the sympatho-excitatory effects of ouabain and CSF sodium.