Inhibition of cytochrome P450 4A decreases arterial pressure without affecting water balance in SHR

Cytochrome P450 4A (CYP) is overexpressed in Spontaneously Hypertensive Rats (SHR) and has been implicated as a contributor to hypertension. While studies have focused on whether CYP overexpression increases resistance in the renal vasculature, subsequently decreasing GFR and renal water handling, research has not investigated whether CYP inhibition alters water balance in SHR. The present study examined the time course of CYP inhibition on blood pressure and whether CYP inhibition alters water balance in SHR. 8–12 week old SHR were chronically instrumented with telemetry probes and housed in metabolic cages for measurement of water intake, urine output and resulting water balance. Following a six‐day control period, 1‐aminobenzotriazole (ABT) was injected (50 mg/kg; i.p.) to inhibit CYP activity. ABT significantly reduced blood pressure with peak decreases occurring within 3 hours of administration. However, ABT did not affect 24‐hour net water intake, urine output or net water balance. These results suggest that CYP overexpression affects arterial pressure by elevating systemic peripheral resistance versus altering renal control of water balance. (NIH #1 R15 HL081109‐01)