Pelvic venous congestion (PC) is thought to be related to several diseases of the lower urinary tract (LUT). We examined the characteristics of the LUT in rats with PC. To create PC, female rats were anesthetized with isoflurane, and the bilateral common iliac veins and bilateral uterine veins were ligated. At 1–8 weeks after either ligation or sham surgery, we performed cystometry with or without administration of carbazochrome sodium sulfonate hydrate or propiverine hydrochloride, histologic examination of the bladder, blood flow imaging, assessment of locomotor activity, measurement of urinary 8-hydroxydeoxyguanosine (8-OHdG) and nitric oxide metabolites (NOx), and the Evans blue dye extravasation test. PC elevated frequency of urination after 2–6 weeks, and caused a decrease of spontaneous locomotor activity. In addition, there was a decrease of bladder blood flow, an increase of bladder vascular permeability, an increase of urinary 8-OHdG, a decrease of urinary NOx, and mild inflammatory changes of the bladder. In rats with PC, frequency of urination was normalized by administration of propiverine or carbazochrome. Rats with PC may be used as a model of PC associated with high frequency of urination, and this model may be useful when developing treatment for LUT symptoms associated with PC.
Transient receptor potential vanilloid 1 (TRPV1) is a nociceptive cation channel that is activated by heat, protons and chemical ligands such as capsaicin. We investigated the roles of the capsaicin receptor, TRPV1, in controlling the energy metabolism of the whole body. It has been reported that the activation of TRPV1 by its agonists enhances energy metabolism. In this study, we used a respiratory gas analysis system to examine whether the inhibition of TRPV1 changes energy metabolism in mice. In addition, we examined the contributions of different modes of TRPV1 activation (heat, protons and capsaicin) to determine the influence of 3 different TRPV1 antagonists on energy metabolism. Here, we showed that intragastric administration of AMG517, a nonselective antagonist of TRPV1 (for heat, protons and capsaicin), enhanced energy metabolism as much as did intraperitoneal administration. On the other hand, intraperitoneal administration of AMG9810, a nonselective antagonist like AMG517, enhanced energy expenditure more than intragastric administration. However, the administration of JYL1421, a TRPV1 antagonist that very strongly inhibits TRPV1 activated by capsaicin, did not change energy metabolism. Taken together, these results suggest that the type of TRPV1 antagonists and the routes of its administration have different effects on energy metabolism in a normal body. Surprisingly, co-administration of JYL1421 and capsaicin significantly enhanced the energy metabolism more than administration of capsaicin alone. These results support the possibility that an unconventional mechanism is responsible for the increase in energy metabolism that occurs via TRPV1 inhibition.
Peripheral nerve injury has been suggested to up-regulate mRNA for the vascular endothelial growth factor (VEGF) which enhances nerve regeneration. VEGF is known to regulate angiogenesis by binding with a specific receptor, the vascular endothelial growth factor receptor (VEGFR). However, little is known about the involvement of VEGF-VEGFR signaling in the nerve regeneration at early stages though previous studies contained a lengthy observation. The present study examined that relationship between angiogenesis and peripheral nerve regeneration at the early stage after nerve transection by focusing on the chronological changes in the expression patterns of VEGF-VEGFR signaling. This study used our previously reported experimental model for nerve regeneration following the transection of the inferior alveolar nerve (IAN) in mice. In a double staining of PGP9.5 and CD31, respective markers for the nerve fibers and endothelial cells, CD31 immunoreactions first appeared in the injury site on postoperative (PO) day 2 when the transected nerve fibers had not been re-connected. The most intense immunoreaction for CD31 was found around the regenerating nerve fibers extending from the proximal stump on PO day 3, but it gradually lessened to disappear by PO day 7. The expression patterns of VEGFR1 and VEGFR2 showed similar chronological changes through the observation periods, with most intense immunoreaction found on PO day 3. Western blotting of total protein extracted from the injury site demonstrated the clear bands for VEGF-A and VEGF-B on PO day 2, indicating a time lag for the expression of ligands and receptors. A local administration of antibody to VEGF-A inhibited the elongation of the nerve fibers from the proximal stump. Furthermore, this administration of VEGF-A antibody inhibited the expression of CD31 in the gap between proximal and distal stumps. These results indicated that a nerve injury initiates productions in VEGF-A and VEFG-B, followed with the expression of VEGFR1 and VEGFR2 at early stages after the nerve injury. Taken these findings together, it is reasonable to postulate that immediate response of VEGF-VEGFR signaling to nerve injury plays a crucial role in local angiogenesis, resulting in a trigger for the regeneration of the nerve fibers in mouse IAN.
Class B scavenger receptor family members, scavenger receptor B1 (SR-B1) and cluster of differentiation 36 (CD36), are broadly expressed cell-surface proteins, both of which are believed to serve as multifaceted players in lipid and lipoprotein metabolism in mammals. Because of its presence in the apical part of taste receptor cells within circumvallate taste buds and its ability to recognise long-chain fatty acids, CD36 has been believed to participate in the sensing of the lipid species within the oral cavity. However, there have been no attempts to address whether SR-B1 has such a role to date. In this study, by reverse transcription- polymerase chain reaction analysis, we detected SR-B1 mRNA in a total RNA sample isolated from the circumvallate papillae of mouse tongue. Immunohistochemical analysis of tongue sections from the animals revealed the expression of SR-B1 protein in a population of taste bud cells of circumvallate papillae. In addition, the pattern of staining in the papillae for SR-B1 agreed closely with that for CD36 in double immunostaining analysis. We performed a cell-free in-vitro assay utilising a peptide mimic of SR-B1 and provided evidence that the receptor could recognise certain of the unsaturated long-chain fatty acids such as oleic acid. Our present findings suggest an additional role for SR-B1 as a captor of specific fatty acids in the oral cavity of mammals and contribute to expanding our knowledge of the physiological function of the receptor.