Progesterone reduces erectile dysfunction in sleep-deprived spontaneously hypertensive rats

Abstract

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.

Conclusion: 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.

Figure 1

Schematic representation of the groups used in the present study. In Experiment 1, four groups of paradoxical sleep-deprived (PSD) animals each were studied: Wistar-saline; Wistar-cocaine; SHR-saline and SHR-cocaine; another set of home-cage control (CTRL) and PSD of SHR and Wistar strains were used for hormonal assessment. Experiment 2: hormone-treatment SHR groups were used: vehicle; 25 mg/kg or 50 mg/kg of progesterone; 0.5 mg/kg or 1 mg/kg of testosterone. After the PSD period each group was then subdivided into saline or cocaine-challenged groups.

Figure 2

Effect of i.p. saline or i.p. cocaine (7 mg/kg) on genital reflexes in paradoxical sleep deprived Wistar and SHR rats. Panel A: Percentage of rats displaying genital reflexes and Panel B: Frequency of genital reflex events. *Different from same-strain (saline); ^#Different from the respective group of Wistar strain. In Panel B, data are expressed as mean ± SEM for N = 10. Abbreviations: PE: penile erection; EJ: ejaculation; W: Wistar; SHR: spontaneously hypertensive rats.

Figure 3

Mean ± SEM concentrations of serum testosterone (in ng/mL, panel A), and progesterone (in ng/mL, panel B) in control (CTRL) and paradoxical sleep deprivation (PSD) male rats. *Different from same-strain control rats; ^#Different from the respective group of Wistar strain.

Figure 4

Effect of progesterone treatment (in mg/kg) on genital reflexes in paradoxical sleep deprived SHR. Panel A: Percentage of rats displaying genital reflexes and Panel B: Frequency of genital reflexes events. *Different from same-strain (saline); ^#Different from Wistar strain (cocaine); ^¥Different from Wistar strain (saline). ^§Different from SHR+vehicle group; ^‡Different from SHR+25 mg/kg+cocaine of progesterone. In Panel B, data are expressed as mean ± SEM for N = 10.

Figure 5

Effect of testosterone treatment (in mg/kg) on genital reflexes in paradoxical sleep deprived SHR. Panel A: Percentage of rats displaying genital reflexes and Panel B: Frequency of genital reflex events. *Different from same-strain (saline); ^#Different from Wistar strain (cocaine); ^¥Different from Wistar strain (saline). In Panel B, data are expressed as mean ± SEM for N = 10 (SHR+T 1 mg/kg+cocaine, N = 9).