Prostate apoptosis after doxazosin treatment in the spontaneous hypertensive rat model.
OBJECTIVE
To validate the spontaneous hypertensive rat (SHR) model for basic research into benign prostate hyperplasia (BPH), and to assess doxazosin-induced changes in prostatic structure and apoptotic status.


METHODS
Four groups of rats were assessed: group 1, 15 SHRs treated with doxazosin; group 2, 14 SHRs with unilateral excision of the major pelvic ganglion; group 3, 14 untreated SHRs; and group 4, 16 intact Wistar-Kyoto (WKY) rats. The doxazosin mesylate (0.03 mg daily) was given compacted in rat food for 3 months. The prostatic ventral lobe (VL) was excised and weighed. Stereological light microscopy, multiplex reverse transcription-polymerase chain reaction of prostate caspases, and caspase-3 activity (cellular enzymatic assay) were assessed.


RESULTS
There was more development of the glandular epithelium (P < 0.001) in SHR rats than in controls, which was even greater after doxazosin exposure (P = 0.027). SHR animals had higher caspase expression (P < 0.05) and activity (P = 0.008) than WKY rats, but both were reduced after doxazosin therapy (P < 0.01 and 0.028, respectively).


CONCLUSIONS
This study confirmed prostate hyperplasia in the SHR model. Doxazosin exposure did not reduce the volume of glandular epithelium and contributed to protecting against caspase-induced apoptosis. The SHR model may be not a valid option to study doxazosin-induced apoptosis in BPH.
Lujan
M
M
Department of Urology, Hospital de Getafe, Madrid, Spain. marcos.lujan@terra.es
Ferruelo
A
A
Paez
A
A
Moreno
A
A
Berenguer
A
A
D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D015331:Cohort Studies; D017292:Doxazosin / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008297:Male; D011470:Prostatic Hyperplasia / Q000201:enzymology / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D000959:Antihypertensive Agents; D012333:RNA, Messenger; D020169:Caspases; D017292:Doxazosin