Inhibition of Central Sympathetic and Somatic Outflow to the Lower Urinary Tract of the Cat by the Alpha sub 1 Adrenergic Receptor Antagonist Prazosin

Abstract

Selective alpha sub 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 prostate might also contribute to their effectiveness. The present experiments examined the effects of the selective alpha 1 adrenergic receptor antagonist prazosin on sympathetic activity recorded from the hypogastric 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 spontaneous activity recorded from the hypogastric nerve (to 65 percent of control) and reduced evoked reflex activity recorded from the hypogastric nerve (to 44 percent of control) and the pudendal nerve (to 48 percent of control). Interestingly, when the urinary bladder was filled, the inhibitory effects of prazosin on the pelvic to hypogastric reflex were overcome. These experiments indicate that central noradrenergic neurons mediate a tonic facilitation of sympathetic and somatic activity to pelvic viscera via activation of alpha sub 1 adrenergic receptors. Thus, alpha 1 adrenergic receptor antagonists may reduce the dynamic component of urethral outlet obstruction in patients with benign prostatic hyperplasia through dual mechanisms: first, through a blockade of alpha 1 adrenergic receptors on the prostatic smooth muscle itself and, second, by reducing the activity of the sympathetic neurons that innervate the prostate. Additional therapeutic relief may be provided through reduction of somatic neural activity to the external urethral sphincter, which might also reduce outlet resistance and improve flow.