Effects of chronic stress on bladder morphology of rats and impact of comfort food diet as an ameliorating agent.

OBJECTIVES: To investigate the effects of chronic stress on bladder morphology and the impact of food preference (standard or comfort foods) on the bladder of stressed rats. METHODS: In total, 32 Wistar male rats (3 months old) were divided into four groups: control (C), stressed (S), control + comfort food (C + CF), and stressed + comfort food (S + CF). Groups C and C + CF were maintained under normal conditions, while groups S and S + CF were subjected to chronic stress by the restraint method. Groups C and S received standard rat chow, while groups C + CF and S + CF received comfort food (Froot Loops®) and standard chow. The stress stimuli were induced daily for 2 h over 8 weeks. After 8 weeks, all animals were killed, and the bladders were removed and used for histomorphometric analysis. RESULTS: Body mass was similar among the groups. Stress did not promote differences regarding food intake, but animals receiving comfort food showed higher calories intake (in kcal/Kg) than animals receiving only standard chow. The C + CF and S + CF groups preferred comfort food over the standard chow; this preference was higher in the S + CF than in the C + CF group. The surface density of smooth muscle was reduced in stressed animals, while connective tissue and elastic system fiber content were increased in stressed groups. Further, epithelial height was increased in rats submitted to chronic stress. The surface density of elastic system fibers was decreased by the consumption of comfort food. CONCLUSIONS: Chronic stress induces morphological modifications on the bladder wall and epithelium. These modifications may be related to lower urinary tract symptoms. Additionally, chronic stress caused a higher preference for comfort food intake which did not ameliorate or aggravate the stress-induced bladder alterations.

Effects of dutasteride and tamsulosin on penile morphology in a rodent model.

PURPOSE: To evaluate the penile morphology after the isolated and combined administration of dutasteride and tamsulosin in a rodent model. MATERIALS AND METHODS: Forty male rats were assigned into the following groups: Control group (C, receiving distilled water, n=10); Dutasteride group (D, receiving 0.5 mg/Kg/day of dutasteride, n=10); Tamsulosin group (T, receiving 0.4 mg/Kg/day of tamsulosin, n=10); and Dutasteride associated with Tamsulosin group (DT, receiving both drugs n = 10). All drugs were administered via oral gavage. After 40 days, the animals were submitted to euthanasia and their penises were collected for histomorphometric analyses. Data were compared using one-way ANOVA followed by Bonferroni's post-test, considering p<0.05 as significant. RESULTS: The sinusoidal space and smooth muscle fiber surface densities (Sv), and the cross-sectional penile areas of rats in groups D, T and DT were reduced in comparison to controls with the most notable reductions in the combined therapy group. The connective tissue and elastic system fibers Sv were augmented in groups D, T and DT in comparison with the control group, again with the most pronounced changes observed in animals receiving the combined therapy. CONCLUSION: Both treatments with dutasteride or tamsulosin promoted penile morphometric modifications in a rodent model. The combination therapy resulted in more notable modifications. The results of this study may help to explain the erectile dysfunction observed in some men using these drugs.

Amyloid-ß Processing in Aged S100B Transgenic Mice Is Sex Dependent.

(1) Background: Calcium-binding protein S100B is involved in neuroregeneration but has also been associated with neurodegeneration. These contrasting effects may result from concentration or duration of exposure. We investigated the effect of long-term increased S100B levels on amyloid-ß processing in one-year-old transgenic (tg) mice with 12 copies of the murine S100B gene with specific consideration of sex and specific brain regions. (2) Methods: S100B and amyloid-ß 42 (Aß42) were quantified in serum, cerebrospinal fluid (CSF), adipose tissue, and different brain regions by ELISA in wild-type (wt) and S100Btg mice (each n = 7 per group). Thioflavin T (ThT) and Aß immunostaining were performed for visualization of Aß deposition. (3) Results: S100B in serum, CSF, and brain was significantly increased in S100Btg mice of both sexes. Aß42 was significantly increased in the hippocampus of male S100Btg mice (p = 0.0075), and the frontal cortex of female S100Btg mice (p = 0.0262). ThT and Aß immunostaining demonstrated Aß deposition in different brain regions in S100Btg mice of both sexes and female wt. (4) Conclusion: Our data validate this experimental model for studying the role of S100B in neurodegeneration and indicate that Aß processing is sex-dependent and brain region-specific, which deserves further investigation of signaling pathways and behavioral responses.

Quercetin as a nephroprotector after warm ischemia: histomorphometric evaluation in a rodent model.

PURPOSE: To quantitatively evaluate the possible long-term protective effects of quercetin during renal warm ischemia. MATERIALS AND METHODS: Male rats were allocated into 4 groups: sham (S), sham quercetin (SQ), ischemia (I), and ischemia quercetin (IQ). Groups SQ and IQ received quercetin (50mg/kg) before and after surgery. Groups I and IQ had their left renal vessels clamped for 60 minutes. All animals were euthanized four weeks after the procedure, and serum urea and creatinine levels were measured. Renal weight and volume, cortex-non-cortex area ratio (C-NC), cortical volume (CV), glomerular volumetric density (Vv[glom]), volume-weighted glomerular volume (VWGV) and number of glomeruli per kidney (N[glom]) were evaluated by stereological methods. Results were considered statistically significant when p < 0.05. RESULTS: Serum urea levels in group I increased by 10.4% in relation to group S, but no differences were observed among the other groups. The C-NC of group I was lower than those of all other groups, and group IQ had similar results to sham groups. The Vv[glom] and N[glom] of group I were lower than those of group S (33.7% and 28.3%, respectively) and group IQ had no significant difference compared to the S group. CONCLUSIONS: Quercetin was effective as a nephroprotective agent in preventing the glomerular loss observed when the kidney was subjected to warm ischemia. This suggests that this flavonoid may be used preventively in kidney surgery, when warm ischemia is necessary, such as partial nephrectomy.

Effects of the dutasteride and sildenafil association in the penis of a benign prostatic hyperplasia animal model.

OBJECTIVE: The aim of this study was to investigate whether concomitant treatment of dutasteride and sildenafil could prevent structural changes in the penis of a BPH rodent model. METHODS: Thirty-two adult male rats were divided into the following groups: Ctrl, untreated control rats; BPH, untreated spontaneously hypertensive rats (SHRs); BPH + D, SHRs treated with dutasteride; and BPH + DS, SHRs treated with dutasteride and sildenafil. All treatments were performed during 40 days, following which the penises were collected for histomorphometrical analysis. The results were compared via one-way ANOVA with Bonferroni's post-test, considering p values <.05 as significant. RESULTS: The smooth muscle density decreased by 28.6% and 21.4% in BPH + D and BPH + DS, respectively, when compared to the BPH group. The sinusoid space density reduced by 32.2% in BPH, when compared to the Ctrl group; this density was also reduced by 22.6% in BPH + D, when compared to the BPH group. The density of the elastic fibers increased 51.6% and 65.6% in BPH + D and BPH + DS, when compared to the BPH group. CONCLUSION: Treatment with dutasteride promoted morphological changes in the corpus cavernous of this BPH model. Concomitant treatment with sildenafil did not prevent the morphological changes caused by dutasteride; on the contrary, it also promoted a further increase in elastic fibers.

Anatomical background of ovine kidney for use as animal model: analysis of arterial segmentation, proportional volume of each segment and arterial injury after cranial pole partial nephrectomy.

OBJECTIVE: To study the arterial segments of ovine kidney, present a proportional volume analysis of each kidney arterial segment, and analyze arterial injuries caused by simulated partial nephrectomy of cranial pole. MATERIALS AND METHODS: Forty-eight ovine kidneys injected with polyester resin into the renal arteries and collecting system were used in this study. Eighteen kidneys were used to study the arterial segments and the proportional volume of each renal segment. Other 30 kidneys were submitted to superior pole resection at a distance of 1.0cm, 0.5cm, or exactly at the cranial hilar edge, just before the resin hardening. These endocasts were used to evaluate the arterial injuries caused by these different resection planes. RESULTS: Ovine renal artery divided into two (ventral and dorsal) or three segmental arteries. Dorsal segment presented higher proportional volume than ventral segment. For kidneys with three segments, the third segment was on the caudal region (caudo-ventral or caudo-dorsal segment) and presented the lowest proportional volume. None of the resected kidneys (at 1.0, 0.5 or at the cranial hilar edge) presented injury of arterial branches that irrigate non-resected region. CONCLUSION: The segmental distribution of renal artery, the proportional volume of each segment and arterial injuries after cranial pole resection in ovine kidneys are different from what is observed in human kidneys. Meanwhile, ovine kidneys show a primary segmental division on anterior and posterior, as in humans, but different from swine. These anatomical characteristics should be considered when using ovine as animal models for renal experimental and/or training procedures.

Evaluation of the effects of chronic stress applied from the prepubertal to the adult stages or only during adulthood on penile morphology in rats.

The present study aimed to evaluate the effects of chronic stress from the prepubertal to the adult stages or during adulthood on penile morphology in rats. The animals were immobilized in a cylinder for 2 h daily for a total of six weeks to simulate stress. Ten rats were exposed to stress stimulus beginning from the prepubertal age, while nine rats were exposed to stress stimulus only during adulthood. Animals were killed at 24 h after the last stress session for short-term evaluation (SP-S and SA-S), while other age-matched rats were sacrificed at 6 weeks after the last stress session for long-term evaluation (SP-L and SA-L). Age-matched animals were used as controls (CP-S, CA-S, CP-L and CA-L). After treatment, serum testosterone levels and areas of cavernosum structures were evaluated. We observed no changes in serum testosterone levels after stress treatment. Results revealed that the area of the corpus cavernosum without the tunica albuginea in animals in the SA-S group was 16% lower than that in the CA-S group. The smooth muscle was 31% lower in the SP-L group than in the SP-S group and 42% lower in the SA-S group than in the CA-S group. The elastic fiber system was 48% lower in the SP-L group than in the CP-L group and 59% lower in the SA-S group than in the CA-S group. Chronic stress promoted morphological changes in the rat penis and was significantly more pronounced when the stress occurred throughout the adulthood. Chronically applied single stress stimulus caused greater damage to the penis when induced directly during adulthood than when introduced before puberty to adulthood and could be associated with erectile dysfunction.

Neuroprotective Effects of Guanosine Administration on In Vivo Cortical Focal Ischemia in Female and Male Wistar Rats.

Guanosine (GUO) has neuroprotective effects in experimental models of brain diseases involving glutamatergic excitotoxicity in male animals; however, its effects in female animals are poorly understood. Thus, we investigated the influence of gender and GUO treatment in adult male and female Wistar rats submitted to focal permanent cerebral ischemia in the motor cortex brain. Female rats were subdivided into non-estrogenic and estrogenic phase groups by estrous cycle verification. Immediately after surgeries, the ischemic animals were treated with GUO or a saline solution. Open field and elevated plus maze tasks were conducted with ischemic and naïve animals. Cylinder task, immunohistochemistry and infarct volume analyses were conducted only with ischemic animals. Female GUO groups achieved a full recovery of the forelimb symmetry at 28-35 days after the insult, while male GUO groups only partially recovered at 42 days, in the final evaluation. The ischemic insult affected long-term memory habituation to novelty only in female groups. Anxiety-like behavior, astrocyte morphology and infarct volume were not affected. Regardless the estrous cycle, the ischemic injury affected differently female and male animals. Thus, this study points that GUO is a potential neuroprotective compound in experimental stroke and that more studies, considering the estrous cycle, with both genders are recommended in future investigation concerning brain diseases.

Immediate and Late Effects of Stress on Kidneys of Prepubertal and Adult Rats.

BACKGROUND/AIMS: Stress had been related to physiological and morphological alterations in different organs, however kidney morphology and function after stress conditions are not well-known. To evaluate the effects of chronic stress on renal morphology in prepubertal and adult rats, and to investigate if the effects of induced stress remain stable or worsen following removal of the stress stimuli. METHODS: Forty prepubertal rats (4 weeks old) and thirty six adult rats (10 weeks old) were used. Each age group was divided a into control group and a stressed group. Stressed animals were restrained in rigid tubes 2 hours per day for 6 weeks. Animals were euthanized 24 hours after the last stress stimulus for immediate evaluation (50% of the groups), and 6 weeks after the last stress stimulus for late evaluation (50% of the groups). Kidney weight and volume, cortical-medullar ratio, glomerular volumetric density, volume-weighted glomerular volume, and number of glomeruli per kidney were evaluated using the Image J software. RESULTS: Prepubertal stressed animals showed reduced kidney weight and volume, and increased cortical-medullar ratio in comparison to its control group when evaluated immediately. Furthermore, stressed prepubertal and adult animals evaluated immediately had reduced glomerular volumetric density. Most importantly, all stressed groups exhibited reduced number of glomeruli per kidney. Other analyzed parameters did not difeer significantly the groups. CONCLUSION: Chronic stress induced before and after puberty led to irreversible glomerular loss, however, renal impairment was interrupted by removal of the stress stimuli.

Mannitol reduces nephron loss after warm renal ischemia in a porcine model.

BACKGROUND: Mannitol has been employed to ameliorate renal warm ischemia damage during partial nephrectomy, however, there is limited scientific evidence to support the use of mannitol during partial nephrectomy. The objective of the present study was to investigate the glomerular number after renal warm ischemia, with and without the use of mannitol in a Pig Model. METHODS: Twenty-four male pigs were assigned into three groups. Eight animals were allocated to the sham group that was subjected to laparoscopic dissection of the left renal hilum, without renal ischemia. Eight animals were allocated to the ischemia group that had the left renal hilum clamped for 30 min through laparoscopic access. Eight animals received mannitol (250 mg/kg) before the occlusion of renal hilum for 30 min. The kidneys were collected after the euthanasia of the pigs 21 days post surgery. The right kidney was utilized as a self-control for each animal. Serum creatinine, urea levels, the weight and volume of the kidneys were measured. Glomerular volumetric density, volume-weighted glomerular volume, and cortical volume were quantified through stereological methods and employed to determine the number of nephrons per kidney. Student's t test and ANOVA were used for statistical analysis. RESULTS: In the ischemia group, the left kidney recorded a reduction of 24.6% (290, 000 glomeruli) in the number of glomeruli in comparison to the right kidney. Kidneys subjected to ischemia also displayed decreased weight and volume in comparison to the sham and mannitol groups. No difference was observed between the left and right kidneys from the sham and mannitol groups. Further, no distinction in serum creatinine and urea among the groups was observed. CONCLUSION: The use of mannitol significantly reduces nephron loss during warm ischemia in pigs.

Does a Ureteral Obstruction Affect the Contralateral Kidney Morphology? A Stereological Analysis in a Rodent Model.

OBJECTIVE: To investigate, in a rodent model, the influence of an obstructed kidney/ureter on the contralateral organ morphology. METHODS: Thirty-six rats were randomly assigned into the following groups: untreated ureteral obstruction group (UO-U, n = 10), submitted to a ligature of the ureter at day 0; UO group (at day 0) followed by nephrectomy after 24 h (UO-N, n = 8); nephrectomy group (N, n = 9), submitted to nephrectomy at day 0; and sham group (S, n = 9), submitted to simulated surgery at day 0. All these procedures were performed on the left kidney/ureter. All animals were euthanized 30 days after surgery, and the right kidneys were collected for stereological analysis. Data were compared using a one-way analysis of variance with Bonferroni's post test, considering p < 0.05 as significant. RESULTS: The kidney volume, weight, and cortical volume were augmented in groups UO-N and N, compared to group S. Kidneys from the UO-U group showed only a moderate augmentation in kidney weight, with a reduction in the cortical-medullar ratio, compared to the kidneys in group S. No differences in the glomerular volumetric density, volume-weighted glomerular volume, and number of glomeruli were observed among the right kidneys of the studied groups. CONCLUSION: An obstructed kidney/ureter is more prejudicial to the contralateral kidney morphology than an absent kidney.

What Is the Best Way to Prepare A Buccal Mucosa Graft for Urethroplasty? A Histology-Based Preliminary Report.

PURPOSE: To evaluate the histological characteristics of buccal mucosa samples prepared using different dissection techniques. METHODS: The buccal mucosae harvested from 9 men submitted to a substitution urethroplasty were used in this study. Biopsy specimens of buccal mucosae were grouped according to the macroscopic appearance after dissection: Group 1 - yellowish appearance (minimal dissection), Group 2 - whitish appearance (more aggressive dissection), and Group 3 - translucent appearance (ultra-aggressive dissection). The biopsy specimens were evaluated using histomorphometric techniques. The thicknesses of the graft, epithelium, and sub-epithelial connective tissue were compared. RESULTS: The samples from Group 3 and Groups 2 and 3 presented lower total and lower sub-epithelial connective tissue thickness, respectively, when compared with Group 1. The epithelial thickness was not affected by the dissection method. Muscular and adipose tissues were present in 77 and 55% of samples from Group 1, respectively, whereas these were observed in 44 and 22% of samples from Group 2 respectively. The muscular tissue was observed in 11% of the cases, and the adipose tissue was not observed in samples prepared with ultra-aggressive dissection. CONCLUSION: We conclude that an intermediate graft dissection (whitish appearance, as performed in Group 2) presents the best balance between subepithelial connective tissue preservation and adipose and muscle tissue removal.

Atorvastatin inhibits osteoclastogenesis and arrests tooth movement.

INTRODUCTION: In addition to their cholesterol-lowering effects, the statin class of drugs appears to enhance osteogenesis and suppress bone resorption, which could be a clinical concern during orthodontic treatment. In this animal study, we aimed to determine whether atorvastatin (ATV) affects orthodontic tooth movement (OTM) through osteoclast inhibition. Furthermore, we analyzed the potential adverse effects of ATV on long-bone turnover and endochondral ossification. METHODS: Rats were administered ATV (15 mg/kg) or saline solution via gavage (n = 12 animals/group), starting 2 weeks before initial OTM. Tooth displacement was measured after 7, 14, and 21 days. Histologic sections of the maxilla and femur were obtained after 14 and 21 days of OTM and stained (hematoxylin and eosin; TRAP assay) for histomorphometric analysis. RESULTS: ATV was associated with significant (P <0.05) reductions in OTM and osteoclast counts. Independently of drug administration, OTM increased the number of osteoclasts and reduced the bone-volume ratio compared with the control maxillae without OTM. Long-term statin administration did not appear to affect femoral endochondral ossification. CONCLUSIONS: This experimental study showed that the long-term use of ATV can significantly promote osteoclast inhibition and slow the OTM in the first week in rats. Under physiologic conditions, the drug did not affect bone turnover and endochondral ossification.

Impairment of GABAergic system contributes to epileptogenesis in glutaric acidemia type I.

OBJECTIVES: Glutaric acidemia type I (GA-I) is an inherited neurometabolic disorder caused by deficiency of glutaryl-CoA dehydrogenase (GCDH) and characterized by increased levels of glutaric, 3-OH-glutaric, and glutaconic acids in the brain parenchyma. The increment of these organic acids inhibits glutamate decarboxylase (GAD) and consequently lowers the γ-aminobutyric acid (GABA) synthesis. Untreated patients exhibit severe neurologic deficits during development, including epilepsy, especially following an acute encephalopathy outbreak. In this work, we evaluated the role of the GABAergic system on epileptogenesis in GA-I using the Gcdh-/- mice exposed to a high lysine diet (Gcdh-/- -Lys). METHODS: Spontaneous recurrent seizures (SRS), seizure susceptibility, and changes in brain oscillations were evaluated by video-electroencephalography (EEG). Cortical GABAergic synaptic transmission was evaluated using electrophysiologic and neurochemical approaches. RESULTS: SRS were observed in 72% of Gcdh-/- -Lys mice, whereas no seizures were detected in age-matched controls (Gcdh+/+ or Gcdh-/- receiving normal diet). The severity and number of PTZ-induced seizures were higher in Gcdh-/- -Lys mice. EEG spectral analysis showed a significant decrease in theta and gamma oscillations and predominant delta waves in Gcdh-/- -Lys mice, associated with increased EEG left index. Analysis of cortical synaptosomes revealed a significantly increased percentage of glutamate release and decreased GABA release in Gcdh-/- -Lys mice that were associated with a decrease in cortical GAD immunocontent and activity and confirmed by reduced frequency of inhibitory events in cortical pyramidal cells. SIGNIFICANCE: Using an experimental model with a phenotype similar to that of GA-I in humans-the Gcdh-/- mice under high lysine diet (Gcdh-/- -Lys)-we provide evidence that a reduction in cortical inhibition of Gcdh-/- -Lys mice, probably induced by GAD dysfunction, leads to hyperexcitability and increased slow oscillations associated with neurologic abnormalities in GA-I. Our findings offer a new perspective on the pathophysiology of brain damage in GA-I.

Glomerular Morphology and Renal Function after Warm Ischemia by Main Artery or Selective Clamping in a Porcine Model.

OBJECTIVE: The study aimed to evaluate the ischemic and non-ischemic areas after selective arterial occlusion by using stereological analysis of glomeruli, and to compare them with main arterial clamping and sham-operated animals. MATERIALS AND METHODS: Twenty-four male pigs were used in the study. The animals were divided into 3 groups with 8 animals in each as follows: group sham, submitted to laparoscopic dissection of the renal pedicle but not submitted to ischemia; group arterial (A), submitted to left renal artery clamping; and group selective (S), submitted to left renal artery caudal branch occlusion. Groups A and S underwent 30 min of warm ischemia. Left and right kidneys were collected after 21 days and renal fragments were processed for stereological evaluation. Glomerular volume density (Vv[glom]), mean glomerular volume (MGV), and glomerular density were measured. Serum creatinine and urea were assessed preoperatively, 10 days after surgery, and before euthanasia. RESULTS: There was no significant difference among groups with regard to renal function. Renal weight and volume were similar among groups. Also, no difference was observed between the groups with regard to Vv[glom], MGV, and glomerular density, both when compared to its right control or when left kidneys were compared. CONCLUSIONS: Selective arterial clamping technique was neither superior nor inferior to main artery clamping.

Atorvastatin-induced osteoclast inhibition reduces orthodontic relapse.

INTRODUCTION: The statin class of drugs enhances osteogenesis and suppresses bone resorption, which could be a plausible biologic mechanism for mitigation of orthodontic relapse. We aimed to determine whether atorvastatin (ATV) might affect orthodontic relapse and osteoclastogenesis by modulating expression of RANKL and osteoprotegerin (OPG), crucial molecules involved in bone turnover. Furthermore, we analyzed the adverse effects of ATV on femur turnover and endochondral ossification. METHODS: Wistar rats were subjected to orthodontic tooth movement for 21 days, followed by removal of the appliance and ATV or saline solution administration. Up to 7, 14, and 21 days of ATV administration, tooth relapse was measured, and maxilla and femur sections were obtained and prepared for hematoxylin and eosin, TRAP, and immunohistochemical (RANKL and OPG) staining. RESULTS: ATV decreased tooth relapse (P = 0.03) and osteoclast counts (P = 0.04), which were positively correlated (P = 0.006). Statin administration increased periodontal expression of OPG (P = 0.008), but not of RANKL protein. ATV administration also enhanced growth plate cartilage thickness. CONCLUSIONS: Statin-induced OPG overexpression reduces relapse after orthodontic tooth movement, in a phenomenon correlated with decreased osteoclast counts. This phenomenon sheds light on OPG as a molecular target that modulates maxillary bone metabolism and orthodontic relapse.

The sheep as a model for healing studies after partial nephrectomy.

BACKGROUND: The pig has been considered the best model for renal surgery. However, recent research has demonstrated that the kidney of pigs heals differently from that of humans. The objective of this study was to evaluate sheep as an alternative animal model for studying collecting system healing after laparoscopic partial nephrectomy. MATERIALS AND METHODS: The caudal pole of the left kidney was removed from eight female adult domestic sheep using laparoscopic partial nephrectomy. Monopolar energy was used for hemostasis only in the parenchyma, avoiding coagulation near the collecting system, which was left opened. After 14 d, all animals were euthanized, and their left kidney was removed. Serum levels of urea and creatinine were assessed preoperatively and postoperatively (on days 2, 6, 10, and 14), and peritoneal fluid samples were collected during necropsy for urea and creatinine evaluation. An ex vivo retrograde pyelogram was performed, and a retrograde injection of methylene blue ink was administered to evaluate urinary leakage. Samples from the operated pole were analyzed using histologic methods. RESULTS: During necropsy, an urinoma surrounding the operated kidney was observed in one animal. Peritoneal fluid levels of urea and creatinine were elevated. Retrograde pyelograms exhibited contrast-medium extravasation through the operated pole in all kidneys. The opened collecting system was also confirmed by methylene blue ink injection. The operated pole was covered by collagenous tissue and adhered to adjacent organs. CONCLUSIONS: Sheep should be considered as an adequate experimental model for research on collecting system healing after partial nephrectomy.

Testicular Morphology and Spermatozoid Parameters in Spontaneously Hypertensive Rats Treated with Enalapril.

PURPOSE: We evaluated testicular morphology and spermatozoid parameters in spontaneously hypertensive rats treated with enalapril. MATERIALS AND METHODS: Spontaneously hypertensive rats were assigned to a hypertensive nontreated group and a hypertensive enalapril treated group. Wistar-Kyoto normotensive rats served as controls. Systolic blood pressure was measured weekly. Spermatozoid concentration, motility and viability were determined in samples collected from the epididymal tail. Testicular morphology was analyzed by morphometric methods. All data were compared using ANOVA and the Tukey post test with p <0.05 considered significant. RESULTS: Systolic blood pressure in the enalapril treated group was similar to that in controls but lower than in the nontreated group. Sperm concentration in the enalapril treated group was similar to that in controls and greater than in the nontreated group. Testicular vascular volumetric density decreased in the nontreated group while in enalapril treated rats this parameter was similar to that in controls. Volumetric density of the seminiferous epithelium in the enalapril treated group was higher than in the nontreated group and controls, indicating a possibly positive effect of enalapril on spermatogenesis. CONCLUSIONS: In this animal model hypertension caused morphological changes in the testis and upon spermatozoid production. Enalapril treatment partially protected the testicles from these alterations, restoring normal spermatozoid production.

Penile histomorphometrical evaluation in hypertensive rats treated with sildenafil or enalapril alone or in combination: a comparison with normotensive and untreated hypertensive rats.

INTRODUCTION: Erectile dysfunction (ED) is frequently associated to hypertension and antihypertensive drugs; however, the penile morphological aspects on these situations are poorly known. AIM: Evaluate the penile morphology of untreated hypertensive rats and rats treated with enalapril or sildenafil alone or in combination to verify the hypothesis that morphological alterations promoted by hypertension on corpus cavernosum could be ameliorated by the use of angiotensin-converting enzyme inhibitors and/or phosphodiesterase type 5 inhibitors. METHODS: Fifty male rats were assigned into five groups: normotensive rats, untreated spontaneously hypertensive rats (SHRs), and SHR treated with enalapril or sildenafil alone or in combination. Blood pressure was measured weekly. At the conclusion of the study, the rats were euthanized, and their penises were collected for histomorphometrical analysis. MAIN OUTCOME MEASURES: The cross-sectional areas of the penis, tunica albuginea, and corpus cavernosum were measured. The density of the corpus cavernosum structures was quantified. RESULTS: Both groups of SHR rats treated with enalapril became normotensive. Untreated SHR showed no difference in penile and cavernosal cross-sectional area compared with normotensive rats; however, those rats treated with enalapril or sildenafil alone demonstrated an increase in these parameters. Rats receiving combination therapy showed no cross-sectional area differences compared with normotensive rats. Cavernosal connective tissue density was increased, while the sinusoidal spaces were diminished in untreated SHR. All treatments were effective in maintaining connective tissue density in comparison with normotensive animals. Cavernosal smooth muscle density was similar in all groups, with the exception of the combination therapy group, which demonstrated a reduction in smooth muscle. CONCLUSIONS: Hypertension promoted structural alterations in the corpus cavernosum that may be related to ED. Enalapril- and sildenafil-treated animals had preservation of normal corpus cavernosum structure and an increase in penile and cavernosal cross-sectional area. The combination of these drugs showed less benefit than individual use.

Effect of antioxidants on outcome of testicular torsion in rats of different ages.

PURPOSE: We assessed reproductive and testicular function in adult rats after testicular torsion created before, during and after puberty, and with vs without resveratrol or arginine treatment. MATERIALS AND METHODS: Age matched rats were divided into groups, including simulated surgery without testicular torsion, 720-degree testicular torsion for 4 hours, testicular torsion with resveratrol treatment and testicular torsion with arginine treatment. To study reproductive function at age 12 weeks each rat mated with 3 females. The males were sacrificed at age 14 weeks. Spermatozoids were collected from the epididymal tail and evaluated for concentration, motility and viability. Testicular samples were collected for morphological analysis. RESULTS: Reproductive function was not altered by testicular torsion but antioxidants improved potency. Compared to sham operated and contralateral samples all spermatozoid parameters from testicular torsion samples were inferior. Resveratrol and arginine did not improve spermatozoid quality or quantity in torsed testes but contralateral samples were improved by each drug. The seminiferous epithelium of rats submitted to testicular torsion during puberty was least affected. Each antioxidant partially to totally prevented the morphological alterations found in rats with untreated testicular torsion. Rats submitted to testicular torsion before puberty that were treated with antioxidants showed the fewest changes. CONCLUSIONS: Testicular morphology was altered less in rats when torsion occurred earlier in life, that is during puberty. Treatment with antioxidants improved contralateral spermatozoid production and some fertility parameters. Each antioxidant also prevented testicular morphology alterations after testicular torsion. Prepubertal rats benefited most from antioxidant treatment.