Cytochrome P450 4a Overexpression Increases Both Renal And Non‐Renal Vascular Resistance In SHR

Cytochrome P450 4A (CYP) is overexpressed in Spontaneously Hypertensive Rats (SHR), and our previous study suggests that CYP overexpression contributes to hypertension in SHR by increasing systemic vascular resistance. However, it is unclear whether elevated resistance is localized to the renal vasculature or if overexpression also alters resistance in non‐renal vasculature. To investigate this question, 8–12 week old male SHR were anesthetized and doppler flow probes placed on the renal and superior mesenteric arteries, and a telemetry probe inserted into the descending aorta. Blood flow, arterial pressure and heart rate data were recorded for a one‐hour control period, after which the CYP inhibitor 1‐aminobenzotriazole (ABT 50 mg/kg; i.v.) was injected and data recorded for an additional hour. ABT treatment lowered mean arterial pressure and significantly reduced both renal arterial blood flow (−50.5%) and superior mesenteric arterial flow (−63.5%). Heart rate was unaffected by ABT. These results suggest that CYP overexpression contributes to hypertension in SHR through vasoconstrictive actions in both renal and non‐renal vascular beds. (NIH #1R15HL081109‐01)