Yono Makoto, Yamamoto Yasuhiro, Imanishi Aya, Yoshida Masaki, Ueda Shoichi, Latifpour Jamshid
Department of Urology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
J Recept Signal Transduct Res. 2008;28(4):403-12. doi: 10.1080/10799890802176626.
We compared the effects of two alpha(1)-adrenoceptor antagonists with different selectivity for the alpha(1)-adrenoceptor subtypes, prazosin and naftopidil, on pelvic blood flow and nitric oxide synthase (NOS) levels in the spontaneously hypertensive rat (SHR). SHRs and normotensive Wistar-Kyoto (WKY) rats were distributed initially in four groups: group 1 received prazosin, a subtype nonselective alpha(1)-adrenoceptor antagonist (2 mg/kg/day); group 2 received naftopidil, a selective alpha(1A/D)-adrenoceptor antagonist (10 mg/kg/day); group 3 received cyclazosin, a selective alpha(1B)-adrenoceptor antagonist (5 mg/kg/day); and group 4 received the vehicle orally for 4 weeks. Pelvic blood flow was determined by using a fluorescent microsphere infusion technique. Expression levels of nNOS and eNOS mRNAs in the rat genitourinary tissues were quantified by real-time reverse transcription polymerase chain reaction (RT-PCR) using SYBR Green I. The characteristics of alpha(1)-adrenoceptors in the rat iliac artery were determined by using radioligand receptor binding and real-time RT-PCR techniques. Untreated SHRs had lower blood flow to the ventral prostate, dorsolateral prostate, urinary bladder, and penis and lower mRNA expression levels of nNOS in the bladder and penis and eNOS in the penis than untreated WKY rats. Naftopidil had no significant effects on blood flow and NOS levels, whereas administration of prazosin and cyclazosin to the SHR caused a significant increase in blood flow to each tissue studied and a significant increase in expression levels of these genes. The density of total alpha(1)-adrenoceptors was significantly higher in iliac arteries of untreated SHRs than those of untreated WKY rats. RT-PCR data indicated that alpha(1B)-adrenoceptor mRNA was the significantly predominant gene transcript in iliac arteries of untreated SHRs. Our data show that prazosin, but not naftopidil, causes differential alterations in NOS levels in the SHR genitourinary tract, which could be due to increased pelvic blood flow resulting from inhibiting the vascular alpha(1B)-adrenoceptor. These findings may provide insight into the beneficial effects of subtype nonselective alpha(1)-adrenoceptor antagonists on prostate, bladder, and penile function, when used to treat symptoms of benign prostatic hyperplasia and elevated blood pressure.
我们比较了两种对α1 -肾上腺素能受体亚型具有不同选择性的α1 -肾上腺素能受体拮抗剂——哌唑嗪和萘哌地尔，对自发性高血压大鼠（SHR）盆腔血流及一氧化氮合酶（NOS）水平的影响。将SHR和正常血压的Wistar - Kyoto（WKY）大鼠最初分为四组：第1组给予哌唑嗪，一种非选择性α1 -肾上腺素能受体拮抗剂（2毫克/千克/天）；第2组给予萘哌地尔，一种选择性α1A/D -肾上腺素能受体拮抗剂（10毫克/千克/天）；第3组给予环唑嗪，一种选择性α1B -肾上腺素能受体拮抗剂（5毫克/千克/天）；第4组口服赋形剂，持续4周。采用荧光微球灌注技术测定盆腔血流。使用SYBR Green I通过实时逆转录聚合酶链反应（RT - PCR）对大鼠泌尿生殖组织中nNOS和eNOS mRNA的表达水平进行定量。采用放射性配体受体结合和实时RT - PCR技术测定大鼠髂动脉中α1 -肾上腺素能受体的特性。未治疗的SHR与未治疗的WKY大鼠相比，其腹侧前列腺、背外侧前列腺、膀胱和阴茎的血流较低，膀胱和阴茎中nNOS的mRNA表达水平以及阴茎中eNOS的mRNA表达水平较低。萘哌地尔对血流和NOS水平无显著影响，而给SHR给予哌唑嗪和环唑嗪导致所研究的每个组织的血流显著增加以及这些基因的表达水平显著增加。未治疗的SHR的髂动脉中总α1 -肾上腺素能受体的密度显著高于未治疗的WKY大鼠。RT - PCR数据表明，α1B -肾上腺素能受体mRNA是未治疗的SHR的髂动脉中显著占主导的基因转录本。我们的数据表明，哌唑嗪而非萘哌地尔会导致SHR泌尿生殖道中NOS水平的差异变化，这可能是由于抑制血管α1B -肾上腺素能受体导致盆腔血流增加所致。这些发现可能为非选择性α1 -肾上腺素能受体拮抗剂在用于治疗良性前列腺增生症状和高血压时对前列腺、膀胱和阴茎功能的有益作用提供见解。
