Differential effects of prazosin and naftopidil on pelvic blood flow and nitric oxide synthase levels in spontaneously hypertensive rats.
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.
Yono
Makoto
M
Department of Urology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. yonomakoto@hotmail.com
Yamamoto
Yasuhiro
Y
Imanishi
Aya
A
Yoshida
Masaki
M
Ueda
Shoichi
S
Latifpour
Jamshid
J
D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D006973:Hypertension / Q000201:enzymology / Q000503:physiopathology*; D008297:Male; D009281:Naphthalenes / Q000008:administration & dosage / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010388:Pelvis / Q000098:blood supply*; D010413:Penis / Q000098:blood supply* / Q000187:drug effects; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011224:Prazosin / Q000008:administration & dosage / Q000494:pharmacology*; D011467:Prostate / Q000098:blood supply* / Q000187:drug effects; D011799:Quinazolines / Q000008:administration & dosage / Q000494:pharmacology; D011810:Quinoxalines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects; D001743:Urinary Bladder / Q000098:blood supply* / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D009281:Naphthalenes; D010879:Piperazines; D011799:Quinazolines; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; C080462:cyclazosin; D019001:Nitric Oxide Synthase; C064357:naftopidil; D011224:Prazosin