Abstract 041: Brain Cytochrome P450 1B1-Testosterone Generated Metabolite 6Beta-Hydroxytestosterone Contributes to Angiotensin II-Induced Increased Sympathetic Outflow and Blood Pressure

Cytochrome P450 1B1 (CYP1B1)-generated testosterone (T) metabolite 6β-hydroxytestosterone (6β-OHT) contributes to angiotensin (Ang) II-induced hypertension in the male mice. However, the site of action of CYP1B1-testosterone metabolite 6β-OHT in Ang II-induced hypertension is unknown. The demonstration that Ang II increases blood pressure by its action in the subfornical organ and the presence of CYP1B1 in the brain led us to hypothesize that T contributes to Ang II-induced hypertension via its metabolism to 6β-OHT in the brain. To test this hypothesis, we examined the effect of intracerebroventricularly (ICV) administered T in castrated (Cas) wild-type (Cyp1b1+/+) and Cas Cyp1b1-/- mice on the action of systemic Ang II (700 ng/kg/min) for 14 days. T (3 μg/2μL/injection/every 2nd day) or its vehicle (2-Hydroxypropyl-β-cyclodextrin dissolved in artificial CSF) was injected via a cannula implanted in the brain. Mean arterial blood pressure (MAP, mmHg) was measured by radiotelemetry (n=4-5). Ang II increased...