PHARMACOLOGICAL ANTAGONISM OF ALPHA-ADRENERGIC AGONIST-INDUCED INCREASES IN CANINE INTRAURETHRAL PRESSURE IN-VIVO

Treatment with a, antagonists represents a pharmacological alternative to surgery for the treatment of urinary obstruction associated with b enign prostatic hyperplasia (BPH). A minimally invasive method to meas ure elevation of prostatic urethral tone through a urethral catheter w as used to study the effect of alpha-adrenoceptor agonists and antagon ists on canine intraurethral pressure (IUP). alpha(1)-adrenoceptor ago nists, but not alpha(2) agonists, elicited elevations in IUP. The cont ractile response was primarily the result of prostatic smooth muscle c ontraction, since it was of smaller magnitude in female dogs or in mal e dogs outside of the prostatic urethra. The contractile responses to epinephrine obtained in the absence of antagonist on the same or diffe rent test dates were highly reproducible in dogs greater than 2 years of age. The increase in I UP caused by epinephrine was specifically an tagonized by alpha(1)-adrenoceptor antagonists, in direct proportion t o their potency in isolated canine prostatic strips in vitro and in pr oportion to their affinity at receptors determined in radioligand bind ing assays in vitro. These data confirm the role of alpha(1)-adrenocep tors in canine prostatic smooth muscle contraction and this relatively non-invasive in vivo model will allow the study of novel compounds fo r their effects on canine prostatic tone. (C) 1995 Wiley-Liss, inc.