Biomedical subjects

H H Davila

Publications and source records attributed to H H Davila.

3 recordsLinked to original sources

PubMed2004

Corporal veno-occlusive dysfunction in aging rats: evaluation by cavernosometry and cavernosography.

OBJECTIVES: To determine whether the rat develops corporal veno-occlusive dysfunction (CVOD) during the aging process. METHODS: We divided male Fisher 344 rats into four groups with 5 to 8 rats in each group. Group 1 rats were 5 months old and not orchiectomized (young intact); group 2 were 5 months old and had undergone castration (control CVOD); group 3 were 24 months old and not orchiectomized (aged intact); and group 4 rats were 24 months old, nonorchiectomized rats who had undergone deep dorsal vein (DDV) ligation (aged ligated). Serum testosterone was measured, and dynamic infusion cavernosometry and cavernosography (by dual-energy x-ray absorptiometry scan) were performed. RESULTS: Compared with the young intact animals, the aged intact rats had a 73% reduction in testosterone, a 30% reduction in intracavernosal pressure after papaverine injection, and an 84% and a 44% increase in the maintenance and drop rate, respectively, during dynamic infusion cavernosometry. The extent of CVOD as measured by cavernosometry in the aged rats was similar to that in the young castrated rats, but was more pronounced when measured by dynamic infusion cavernosometry. Cavernosography confirmed that the aged rats had venous leakage primarily by way of the DDV. By applying DDV ligation, distal penile engorgement occurred, showing that a small venous leakage occurred primarily by way of the cavernosal veins. CONCLUSIONS: These data have demonstrated that CVOD occurs in the aged rat, mainly through the DDV. This supports the concept that the aged rat is an appropriate animal model to study erectile dysfunction associated with CVOD.

Absorptiometry, Photon↗

PubMed2003

Fibrin as an inducer of fibrosis in the tunica albuginea of the rat: a new animal model of Peyronie's disease.

OBJECTIVES: To investigate the role of fibrin in inducing fibrosis in the tunica albuginea (TA) of the rat penis, to develop a new animal model for Peyronie's disease (PD). MATERIALS AND METHODS: The TA of rats (five per group per period) were injected with either saline, fibrin, transforming growth factor-beta1 (TGF-beta1) or TGF-beta1 plus fibrin; the rats were killed at 1, 3, and 6 weeks after injection. Images were analysed quantitatively from tissue sections stained for collagen (Masson trichrome), fibrin (Verhoeff's stain) and elastin (Hart's stain), and immunostained for TGF-beta1, inducible nitric oxide synthase (iNOS), heme oxygenase 1 (HO1), alpha-smooth muscle actin (ASMA), apoptosis (TUNEL) and plasminogen activator inhibitor (PAI). Collagen fibre organization was characterized by electron microscopy. Human PD plaque tissue and normal human TA were assayed for fibrin by immunohistochemistry in nine samples. RESULTS: At 1 week after injection of fibrin into the rat TA, only oedema was present; at 3 weeks, the oedema developed into a characteristic fibrotic PD-like plaque. The injection of TGF-beta1 into the TA also induced oedema in the TA at 1 and 3 weeks but there was very little evidence of a recognisable plaque at either time. Injection with TGF-beta1 plus fibrin resulted in oedema at 1 week but at 3 weeks there was a smaller plaque than with fibrin only. At 6 weeks the induced plaques in the fibrin-only and fibrin + TGF-beta1 groups persisted, and were comparable with those elicited at this time by TGF-beta1 alone. The control animals showed no pathology at any of the sample times. At 3 weeks the PD plaque induced by injection with fibrin alone had not only greater expression of TGF-beta1 than the TA of the animals receiving TGF-beta1 alone, but also greater levels of other markers of fibrosis, e.g. HO1 (reactive oxygen species), ASMA (presence of myofibroblasts), apoptosis, and PAI (inhibitor of fibrinolysis). iNOS, a known antifibrotic agent, was also increased. In human PD plaque tissue, fibrin was detected by immunohistochemistry in all nine specimens. CONCLUSIONS: These results suggest that fibrin, when introduced into the TA of the rat penis, acts as a potential profibrotic protein, possibly via the local release of TGF-beta1, and induces a plaque not only histologically similar to that induced by TGF-beta1 but to that of the human condition. Because fibrin can extravasate from the blood into the human TA after an injury to the TA, and because fibrin persists in the plaque tissue, we hypothesise that fibrin may play a key role in the pathogenesis of human PD.

Animals↗

PubMed2003

Protein inhibitor of nitric oxide synthase (NOS) and the N-methyl-D-aspartate receptor are expressed in the rat and mouse penile nerves and colocalize with penile neuronal NOS.

Nitrergic neurotransmission triggering penile erection is mediated by nitric oxide (NO) synthesized in the cavernosal nerves of the penis by penile neuronal NO synthase (PnNOS). In the central nervous system, nNOS is activated by the N-methyl-D-aspartate receptor (NMDAR) and, presumably, is inhibited by the protein inhibitor of NOS (PIN). The PnNOS and NMDAR are expressed in the penis, and PnNOS has been localized in penile nerves. Both proteins colocalize with PIN in the hypothalamus and the spinal cord involved in the control of erection. The present study aimed to elucidate the relationship between PnNOS, PIN, and NMDAR in the penis. It was found that in the rat, PIN was expressed in the pelvic ganglion and the cavernosal nerve, and penile PIN cDNA was cloned, sequenced, and expressed. Immunohistochemistry localized PIN to the cavernosal and dorsal nerve of the penis, whereas NMDAR was not detected in the latter. Dual-fluorescence labeling showed that PnNOS colocalized with PIN in both nerves but with NMDAR only in the cavernosal nerve. Aging did not affect the mRNA levels of PnNOS, nNOS, NMDAR, and PIN. Both PIN and NMDAR were detected in penile nerves of the wild-type and nNOS(-/-) mouse. The PIN protein did not inhibit or bind NOS in penile extracts, and in vivo, PIN cDNA reduced the erectile response to electrical field stimulation. In conclusion, PIN and NMDAR colocalize with PnNOS in penile nerves, but the functional significance of these protein interactions for penile erection remains to be elucidated.

Aging↗