Effects of different alpha-1 adrenoceptor blockers on proximal urethral function using in vivo isovolumetric pressure changes.
The effects of different alpha-1 adrenoceptor blockers on the urethra and the cardiovascular system were evaluated using an in vivo isovolumetric intra-urethral pressure model in New Zealand white rabbits. The urethra of anesthetized male rabbits was cannulated through the bladder and secured at the vesico-urethral junction. The distal side of urethra under the pubic bone was also closed to allow measurement of the intra-urethral pressure. Both the intra-urethral pressure and the femoral arterial pressure were monitored. The effects of five different alpha-1 adrenoceptor blockers on the increases in both the intra-urethral pressure and blood pressure induced by phenylephrine were then examined. The inhibition rate of the alpha-1 adrenoceptor blockers prazosin, bunazosin, terazosin, alfuzosin and tamsulosin on the increase in intra-urethral pressure caused as a result of contraction by phenylephrine was 87.5 +/- 4.5% (mean +/- S.E.), 88.0 +/- 7.2%, 86.2 +/- 6.2%, 81.4 +/- 4.8% and 92.5 +/- 5.0% respectively. The potency ranking of these alpha-1 adrenoceptor blockers was tamsulosin > bunazosin > prazosin > terazosin > alfuzosin. Their inhibition rate of the arterial pressure increase induced by phenylephrine was 81.9 +/- 5.0%, 86.2 +/- 5.9%, 76.0 +/- 6.0%, 63.6 +/- 5.7% and 58.0 +/- 5.2% respectively, with a potency ranking of bunazosin > prazosin > terazosin > alfuzosin > tamsulosin. We therefore conclude that the alpha-1 adrenoceptor blockers bunazosin and prazosin have a more potent action on both the urethra and the vascular system. However, tamsulosin and alfuzosin displayed a marked blockade of the increased urethral pressure induced by phenylephrine, with much less of a blockade of arterial pressure. In the present study, tamsulosin has been shown to be the most sensitive and powerful of the alpha-1 adrenoceptor blockers on urethral smooth muscle.
Yamaguchi
Takanori
T
Department of Urology, Fukuoka City Medical Center for Sick Children and Infectious diseases, Japan. yamaguchi.t@fukuoka-child.jp
Nagano
Masashi
M
Osada
Yukio
Y
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000031:analogs & derivatives / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D011817:Rabbits; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology; D000077409:Tamsulosin; D014521:Urethra / Q000187:drug effects* / Q000502:physiology
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D011799:Quinazolines; D018340:Receptors, Adrenergic, alpha-1; D013449:Sulfonamides; D010656:Phenylephrine; C041226:Terazosin; C047638:alfuzosin; C018176:bunazosin; D000077409:Tamsulosin; D011224:Prazosin