Progesterone reduces erectile dysfunction in sleep-deprived spontaneously hypertensive rats.
BACKGROUND
Paradoxical sleep deprivation (PSD) associated with cocaine has been shown to enhance genital reflexes (penile erection-PE and ejaculation-EJ) in Wistar rats. Since hypertension predisposes males to erectile dysfunction, the aim of the present study was to investigate the effects of PSD on genital reflexes in the spontaneously hypertensive rat (SHR) compared to the Wistar strain. We also extended our study to examine how PSD affect steroid hormone concentrations involved in genital events in both experimental models.


METHODS
The first experiment investigated the effects of PSD on genital reflexes of Wistar and SHR rats challenged by saline and cocaine (n = 10/group). To further examine the impact of the PSD on concentrations of sexual hormones, we performed a hormonal analysis of testosterone and progesterone in the Wistar and in SHR strains. Since after PSD progesterone concentrations decreased in the SHR compared to the Wistar PSD group we extended our study by investigating whether progesterone (25 mg/kg or 50 mg/kg) or testosterone (0.5 mg/kg or 1.0 mg/kg) administration during PSD would have a facilitator effect on the occurrence of genital reflexes in this hypertensive strain.


RESULTS
A 4-day period of PSD induced PE in 50% of the Wistar rats against 10% for the SHR. These genital reflexes was potentiated by cocaine in Wistar rats whereas this scenario did not promote significant enhancement in PE and EJ in hypertensive rats, and the percentage of SHR displaying genital reflexes still figured significantly lower than that of the Wistar strain. As for hormone concentrations, both sleep-deprived Wistar and SHR showed lower testosterone concentrations than their respective controls. Sleep deprivation promoted an increase in concentrations of progesterone in Wistar rats, whereas no significant alterations were found after PSD in the SHR strain, which did not present enhancement in erectile responses. In order to explore the role of progesterone in the occurrence of genital reflexes, SHR were treated daily during the sleep deprivation period with progesterone; after the administration of this hormone and challenge with cocaine, we observed a significant increase in erectile events compared with the vehicle PSD SHR+cocaine group.


CONCLUSIONS
Our data showed that the low frequency of genital reflexes found in SHR sleep deprived rats may be attributed to the lower concentrations of progesterone in these rats, based on the observation that progesterone replacement increased genital reflexes in this strain.
Andersen
Monica L
ML
Psychobiology Department, Universidade Federal de São Paulo, Escola Paulista de Medicina (UNIFESP/EPM), Napoleão de Barros, Clementino, São Paulo, SP, Brazil. mandersen@psicobio.epm.br
Martins
Raquel C S
RC
Alvarenga
Tathiana A F
TA
Antunes
Isabela B
IB
Papale
Ligia A
LA
Tufik
Sergio
S
D000728:Androgens / Q000097:blood / Q000494:pharmacology; D000818:Animals; D003042:Cocaine; D007172:Erectile Dysfunction / Q000139:chemically induced / Q000188:drug therapy*; D006973:Hypertension / Q000150:complications*; D008297:Male; D011374:Progesterone / Q000097:blood / Q000494:pharmacology*; D011372:Progestins / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D012726:Sexual Behavior, Animal / Q000187:drug effects; D012892:Sleep Deprivation; D013739:Testosterone / Q000097:blood / Q000494:pharmacology; D014662:Vasoconstrictor Agents
D000728:Androgens; D011372:Progestins; D014662:Vasoconstrictor Agents; D013739:Testosterone; D011374:Progesterone; D003042:Cocaine