Effects of alpha 1 inhibition on renal blood flow and sympathetic nervous activity in systemic hypertension.

Doxazosin is a competitive inhibitor of norepinephrine at alpha 1 adrenoceptors on vascular smooth muscle, where it blocks vasoconstriction. Twenty-four patients with mild hypertension were treated with either doxazosin or placebo for 6 weeks. Supine and upright mean arterial pressures decreased by 9 and 12 mm Hg, respectively, in patients receiving doxazosin. This decrease was significantly more than the blood pressure change with placebo (p less than 0.05). Doxazosin therapy led to a small increase in weight (p less than 0.05). It was also associated with a statistically insignificant decrease in renal vascular resistance (568 dynes s/cm5) so that renal blood flow and creatinine clearance did not change. Doxazosin increased renin levels acutely and norepinephrine levels with 6-week treatment, but these changes were not significantly different from placebo. Norepinephrine clearance, measured after a 120-minute infusion of 3H norepinephrine, did not change. Heart rate increased acutely after doxazosin administration, but returned to baseline during 6-week therapy. Blood pressure, measured hourly for 14 hours after treatment, was consistently decreased in all patients. Doxazosin taken once daily lowers blood pressure without affecting renal blood flow or heart rate.