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Pharmacological antagonism of α‐adrenergic agonist induced increases in canine intraurethral pressure in vivo
Author(s) -
Brune Michael E.,
Buckner Steven A.,
Polakowski James,
Kerwin James F.,
Hancock Arthur A.
Publication year - 1995
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430340304
Subject(s) - agonist , antagonism , in vivo , pharmacology , adrenergic , chemistry , adrenergic agonist , endocrinology , medicine , receptor , biology , microbiology and biotechnology
Treatment with α 1 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). α 1 ‐adrenoceptor agonists, but not α 2 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 α 1 ‐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 α 1 ‐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. © 1995 Wiley‐Liss, Inc.