Pharmacological antagonism of α‐adrenergic agonist induced increases in canine intraurethral pressure in vivo

Treatment with α1 antagonists represents a pharmacological alternative to surgery for the treatment of urinary obstruction associated with benign prostatic hyperplasia (BPH). A minimally invasive method to measure elevation of prostatic urethral tone through a urethral catheter was used to study the effects of α‐adrenoceptor agonists and antagonists on canine intraurethral pressure (IUP). α1‐adrenoceptor agonists, but not α2 agonists, elicited elevations in IUP. The contractile response was primarily the result of prostatic smooth muscle contraction, since it was of smaller magnitude in female dogs or in male dogs outside of the prostatic urethra. The contractile responses to epinephrine obtained in the absence of antagonist on the same or different test dates were highly reproducible in dogs greater than 2 years of age. The increase in IUP caused by epinephrine was specifically antagonized by α1‐adrenoceptor antagonists, in direct proportion to their potency in isolated canine prostatic strips in vitro and in proportion to their affinity at receptors determined in radioligand binding assays in vitro. These data confirm the role of α1‐adrenoceptors in canine prostatic smooth muscle contraction and this relatively non‐invasive in vivo model will allow the study of novel compounds for their effects on canine prostatic tone.