Abstract—We have previously shown that a decrease in hypothalamic gamma adducin (&ggr;-adducin) is associated with hypertension in the spontaneously hypertensive rat (SHR). In view of many inherent issues with SHR, our objective in the present study was to provide proof of this concept with the use of 2 nongenetic rat models of hypertension. Subcutaneous angiotensin II (Ang II) infusion for 2 weeks (55 ng/kg per day) resulted in an increase in blood pressure (BP) of 18 mm Hg. This was associated with a 70% decrease in hypothalamic &ggr;-adducin. Concomitant administration of losartan attenuated the development of hypertension and a decrease in &ggr;-adducin. Deoxycorticosterone acetate salt-induced hypertension also caused a 70% decrease in hypothalamic &ggr;-adducin. Finally, neuronal cultures from neonatal rat brains were incubated with 100 nmol/L Ang II for 4 hours to mimic the in vivo Ang II infusion rat model. This chronic incubation with Ang II resulted in a 60% decrease in the neuronal &ggr;-adducin. Taken together, these observations strengthen our hypothesis that a decrease in hypothalamic &ggr;-adducin is linked to hypertension.