Symptomatic bladder outlet obstruction secondary to benign prostatic hyperplasia (BPH) represents one of the most common afflictions of the aging male population. Prostatectomy represents the standard treatment for symptomatic BPH. Although prostatectomy is often considered to be a safe and effective treatment for BPH, incontinence, impotence, ejaculatory dysfunction, stricture formation, bleeding, sepsis, and death are recognized complications associated with this procedure. A significant amount of health care resources are utilized for the surgical treatment of BPH. Medicare reimbursement for prostatectomy in 1990 will approach 1 billion dollars. Nonsurgical treatment of BPH may provide a safe and less costly therapeutic alternative for the treatment of BPH. The long-range objective of this grant proposal is to develop pharmacologic strategies for the treatment of BPH that are directed towards alleviating the specific features of the prostate predisposing to the development of bladder outlet obstruction. It is our hypothesis that the contractile properties of the prostate smooth muscle determines resistence to urinary outflow along the prostatic urethra. Therefore, the smooth muscle content of the prostate, the density of prostate smooth muscle neuroreceptors, the tissue levels of neurotransmitters mediating prostate smooth muscle tone, and the contractile response of prostate smooth muscle to these neuroreceptors, the tissue levels of neurotransmitters mediating prostate smooth muscle tone, and the contractile response of prostate smooth muscle to these neurotransmitters. This grant proposal is designed to identify pharmacological and cytomorphological properties of the human prostate that are associated with the development of bladder outlet obstruction. Since the prostate is a heterogeneous cytomorphometric analysis and biochemical assays for measuring neurotransmitter levels will be compared in different regions of the prostate. The muscarinic cholinergic, alpha adrenergic, serotonin, calcium channel and vasoactive intestinal peptide innervation of the prostate will be investigated since these neurotransmitters have been shown to modulate the contractile properties of smooth muscle. Characterizing the neuropharmacology and cytomorphology of human prostates from men with varying degrees of bladder outlet obstruction may provide the rationale for pharmacologic strategies for the treatment of bladder outlet obstruction in men with BPH.
