Terazosin

Similar to protocol 1, a double-blinded, balanced crossover placebo approach was used. Subjects (n=5) reported to the laboratory on 2 different days separated by a washout period of ≈14 days (Figure S2). Subjects refrained from caffeine, alcohol, and exercise for 24 hours before each experimental day, and the subjects were instructed to eat the same breakfast. An oral dose of either probenecid (3000 mg; Meda) or placebo (800 mg calcium; Orkla Health) was given at ≈08:00 AM. Under aseptic conditions, catheters (20 guage; Arrow, Reading) were placed in the femoral artery and vein of the experimental leg 2 cm below the inguinal ligament under local anesthesia (lidocaine, 20 mg/mL; Astra Zeneca). An oral dose of terazosin (selective α1-adrenergic receptor antagonist, 0.05 mg kg⁻¹; Amdipharm Limited, Ireland) was then given 2 hours after intake of placebo/probenecid. This dosage of terazosin provides ≈80% α1 blockade.^{16 (link)} After additional 2 hours, subjects were placed in the supine position where they received continuous femoral arterial infusion of tyramine (Sigma-Aldrich) for 3 minutes at each dose (0. 15, 0.3, and 1.0 μmol min⁻¹ L leg volume⁻¹). After 30 minutes of rest, continuous femoral arterial infusion of phenylephrine (0.75, 1.5, and 3.0 μg min⁻¹ L leg volume⁻¹; SAD) was performed.