Effects of α1-adrenergic receptor subtype selective antagonists on lower urinary tract function in rats with bladder outlet obstruction

Baojun Gu, Jerome P. Reiter, Debra A. Schwinn, Michael P. Smith, Cees Korstanje, Karl B. Thor, Paul C. Dolber

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Purpose: Antagonists of α1-adrenergic receptors (α1ARs) relieve obstructive and irritative symptoms in patients with bladder outlet obstruction. However, to our knowledge mechanisms underlying the relief of irritative symptoms remain unknown. Because bladder α1dARs are up-regulated in some rats with bladder outlet obstruction, we investigated the effect of the α1aAR antagonist 5-methyl urapidil (5MU) vs the α1a1dAR antagonist tamsulosin on urinary frequency in obstructed rats. Materials and Methods: Baseline frequency was measured using a chronic micturition recording system and then obstruction (40 rats) or sham obstruction surgery (11 rats) was performed. After 6 weeks frequency was reassessed, followed by subcutaneous implantation of osmotic pumps to deliver 5MU, tamsulosin or vehicle for 1 week. Upon the completion of drug treatment urinary frequency was again measured and the pressor response to the α1AR agonist phenylephrine was documented. Results: Obstructed bladder mass was an average of 4.9 times greater than bladder mass in sham operated rats (p <0.001). Urinary frequency was elevated in obstructed rats with a bladder mass of greater than 500 mg vs all rats with a bladder mass of under 255 mg (p = 0.01). Of rats with a bladder mass of greater than 500 mg frequency was decreased in those treated with tamsulosin (p = 0.03) but not in those treated with 5MU. Tamsulosin and 5MU inhibited the pressor response to phenylephrine. Conclusions: Urinary frequency is increased in rats with a bladder mass of greater than 500 mg. The combined α1a1dAR antagonist tamsulosin decreases urinary frequency more than the α1aAR selective antagonist 5MU. This finding supports the hypothesis that the α1dAR is important for mediating irritative symptoms.

Original languageEnglish (US)
Pages (from-to)758-762
Number of pages5
JournalJournal of Urology
Volume172
Issue number2
DOIs
StatePublished - Aug 2004
Externally publishedYes

Fingerprint

Urinary Bladder Neck Obstruction
tamsulosin
Urinary Tract
Adrenergic Receptors
Urinary Bladder
Phenylephrine
Adrenergic Antagonists
Urination
5-methylurapidil

Keywords

  • Bladder
  • Bladder neck obstruction
  • Rats, Sprague-Dawley
  • Receptors, adrenergic, alpha-1
  • Urination

ASJC Scopus subject areas

  • Urology

Cite this

Effects of α1-adrenergic receptor subtype selective antagonists on lower urinary tract function in rats with bladder outlet obstruction. / Gu, Baojun; Reiter, Jerome P.; Schwinn, Debra A.; Smith, Michael P.; Korstanje, Cees; Thor, Karl B.; Dolber, Paul C.

In: Journal of Urology, Vol. 172, No. 2, 08.2004, p. 758-762.

Research output: Contribution to journalArticle

Gu, Baojun ; Reiter, Jerome P. ; Schwinn, Debra A. ; Smith, Michael P. ; Korstanje, Cees ; Thor, Karl B. ; Dolber, Paul C. / Effects of α1-adrenergic receptor subtype selective antagonists on lower urinary tract function in rats with bladder outlet obstruction. In: Journal of Urology. 2004 ; Vol. 172, No. 2. pp. 758-762.
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AU - Gu, Baojun

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AU - Smith, Michael P.

AU - Korstanje, Cees

AU - Thor, Karl B.

AU - Dolber, Paul C.

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AB - Purpose: Antagonists of α1-adrenergic receptors (α1ARs) relieve obstructive and irritative symptoms in patients with bladder outlet obstruction. However, to our knowledge mechanisms underlying the relief of irritative symptoms remain unknown. Because bladder α1dARs are up-regulated in some rats with bladder outlet obstruction, we investigated the effect of the α1aAR antagonist 5-methyl urapidil (5MU) vs the α1a/α1dAR antagonist tamsulosin on urinary frequency in obstructed rats. Materials and Methods: Baseline frequency was measured using a chronic micturition recording system and then obstruction (40 rats) or sham obstruction surgery (11 rats) was performed. After 6 weeks frequency was reassessed, followed by subcutaneous implantation of osmotic pumps to deliver 5MU, tamsulosin or vehicle for 1 week. Upon the completion of drug treatment urinary frequency was again measured and the pressor response to the α1AR agonist phenylephrine was documented. Results: Obstructed bladder mass was an average of 4.9 times greater than bladder mass in sham operated rats (p <0.001). Urinary frequency was elevated in obstructed rats with a bladder mass of greater than 500 mg vs all rats with a bladder mass of under 255 mg (p = 0.01). Of rats with a bladder mass of greater than 500 mg frequency was decreased in those treated with tamsulosin (p = 0.03) but not in those treated with 5MU. Tamsulosin and 5MU inhibited the pressor response to phenylephrine. Conclusions: Urinary frequency is increased in rats with a bladder mass of greater than 500 mg. The combined α1a/α1dAR antagonist tamsulosin decreases urinary frequency more than the α1aAR selective antagonist 5MU. This finding supports the hypothesis that the α1dAR is important for mediating irritative symptoms.

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