INHIBITION OF CENTRAL SYMPATHETIC AND SOMATIC OUTFLOW TO THE LOWER URINARY-TRACT OF THE CAT BY THE ALPHA(1) ADRENERGIC-RECEPTOR ANTAGONIST PRAZOSIN

Selective alpha(1) adrenergic receptor antagonists are used to reduce the dynamic component of urethral obstruction in patients with benign prostatic hyperplasia. Their effectiveness is presumed to result from blockade of alpha(1) adrenergic receptors within the prostatic smooth muscle. However, a reduction in central sympathetic tone to the prosta te might also contribute to their effectiveness. The present experimen ts examined the effects of the selective alpha(1) adrenergic receptor antagonist prazosin on sympathetic activity recorded from the hypogast ric nerve in chloralose-anesthetized cats. For comparison, the effects of prazosin were also examined on somatic activity recorded from the pudendal nerve. When the urinary bladder was empty, prazosin reduced s pontaneous activity recorded from the hypogastric nerve (to 65% of con trol) and reduced evoked reflex activity recorded from the hypogastric nerve (to 44% of control) and the pudendal nerve (to 48% of control). Interestingly, when the urinary bladder was filled, the inhibitory ef fects of prazosin on the pelvic to hypogastric reflex were overcome. T hese experiments indicate that central noradrenergic neurons mediate a tonic facilitation of sympathetic and somatic activity to pelvic visc era via activation of alpha(1) adrenergic receptors. Thus, alpha(1) ad renergic receptor antagonists may reduce the dynamic component of uret hral outlet obstruction in patients with benign prostatic hyperplasia through dual mechanisms: first, through a blockade of alpha(1) adrener gic receptors on the prostatic smooth muscle itself and, second, by re ducing the activity of the sympathetic neurons that innervate the pros tate. Additional therapeutic relief may be provided through reduction of somatic neural activity to the external urethral sphincter, which m ight also reduce outlet resistance and improve flow.