| 1. |
|
|
| 2. |
- Aronsson, Patrik, 1983, et al.
(författare)
-
A novel in situ urinary bladder model for studying afferent and efferent mechanisms in the micturition reflex in the rat.
- 2014
-
Ingår i: Neurourology and urodynamics. - : Wiley. - 1520-6777 .- 0733-2467. ; 33:5, s. 550-557
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS: The search for new animal models to investigate both efferent and afferent levels of the micturition reflex, to better understand urinary dysfunctions, is of great importance. Therefore in this study we developed and characterized, by comparisons with a conventional whole bladder model, a novel in situ model. METHODS: The urinary bladder was carefully prepared and separated, via a midline incision, into two halves all the way to the urethra in pentobarbitone and medetomidine anesthetized male rats. The separated bladder halves (with no direct connection) were immobilized with ligatures to the underlying tissue. The tension could thereafter be recorded at one side, while the other half was occasionally stretched in order to evoke an afferent signal. Also, injections of ATP and methacholine and electric nerve stimulation were employed. RESULTS: Ipsilateral stretch of 30 and 50mN induced a force-dependent contractile response on the contralateral side. Moreover, electrical stimulation of efferent pelvic nerve fibers, and intravenous injections of methacholine and ATP, evoked dose-dependent contractions, resembling responses observed in the whole bladder model. Here, the threshold frequency at electrical stimulation of the efferent fibers was <2Hz and the maximum response appeared at 10-20Hz, while afferent stimulation had a threshold of 5-10Hz with the maximum response at 40Hz. CONCLUSIONS: In the current study we show that stimulation of afferents at one side of the bladder induces, via impulses from the central nervous system, contractions from the other side. This novel model enables quantitative comparisons of changes occurring within the micturition reflex arc in bladder disorders.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Aydogdu, Özgu, 1978, et al.
(författare)
-
Treatment with the soluble guanylate cyclase activator BAY 60-2770 normalizes bladder function in an in vivo rat model of chronic prostatitis.
- 2022
-
Ingår i: European journal of pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 927
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic pelvic pain syndrome (CPPS) is a common and bothersome condition for which no pharmacological treatment options with acceptable efficacy exist. The aim of this study was to investigate the effects of the soluble guanylate cyclase (sGC) activator BAY 60-2770 and the COX-2 inhibitor celecoxib on bladder function in a rat model of CPPS.Forty-eight male Sprague-Dawley rats were intraprostatically injected with either saline, serving as control, or zymosan, to induce prostatitis. On days 8-20, the rats were treated with either dimethylsulphoxide (DMSO; vehicle), celecoxib, BAY 60-2770 or a combination of celecoxib and BAY 60-2770. Thereafter, micturition parameters were assessed in a metabolic cage and urine samples were collected. The following day, cystometry was performed. Subsequently, the urinary bladder and prostate were removed and examined histopathologically.Induction of prostatitis led to a significant increase of micturition frequency and corresponding decrease of volume per micturition. These alterations were ameliorated by celecoxib, and completely normalized by BAY 60-2770. Induction of prostatitis led to a significantly increased number of non-voiding contractions, decreased bladder compliance and increased voiding time. These parameters were normalized by treatment with BAY 60-2770, either alone or in combination with celecoxib. The immunohistochemical analysis showed signs of prostate inflammation, but not bladder inflammation.Induction of prostatitis led to significant impairment in bladder function. These alterations could be prevented by BAY 60-2770, alone or in combination with celecoxib. This is the first study to show that sGC activators could be a promising option for the treatment of CPPS.
|
|
| 7. |
- Cafarchio, EM, et al.
(författare)
-
Oxytocin Reduces Intravesical Pressure in Anesthetized Female Rats: Action on Oxytocin Receptors of the Urinary Bladder
- 2020
-
Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 11:382
-
Tidskriftsartikel (refereegranskat)abstract
- Urinary bladder dysfunction affects several people worldwide and shows higher prevalence in women. Micturition is dependent on the Barrington’s nucleus, pontine urine storage center and periaqueductal gray matter, but other brain stem areas are involved in the bladder regulation. Neurons in the medulla oblongata send projections to hypothalamic nuclei as the supraoptic nucleus, which synthetizes oxytocin and in its turn, this peptide is released in the circulation. We investigated the effects of intravenous injection of oxytocin (OT) on the urinary bladder in sham and ovariectomized rats. We also evaluated the topical (in situ) action of OT on intravesical pressure (IP) as well as the existence of oxytocin receptors in the urinary bladder. In sham female Wistar rats, anesthetized with isoflurane, intravenous infusion of OT (10 ng/kg) significantly decreased the IP (–47.5 ± 1.2%) compared to saline (3.4 ± 0.7%). Similar effect in IP was observed in ovariectomized rats after i.v. OT (–41.9 ± 2.9%) compared to saline (0.5 ± 0.6%). Topical administration (in situ) of 0.1 mL of OT (1.0 ng/mL) significantly reduced the IP (22.3.0 ± 0.6%) compared to saline (0.9 ± 0.7%). We also found by qPCR that the gene expression of oxytocin receptor is present in this tissue. Blockade of oxytocin receptors significantly attenuated the reduction in IP evoked by oxytocin i.v. or in situ. Therefore, the findings suggest that (1) intravenous oxytocin decreases IP due to bladder relaxation and (2) OT has local bladder effect, binding directly in receptors located in the bladder.
|
|
| 8. |
- Daiuto, Sergio A., et al.
(författare)
-
Angiotensinergic and GABAergic transmission in the medial preoptic area: role in urinary bladder and cardiovascular control in female rats
- 2023
-
Ingår i: Frontiers in Physiology. - 1664-042X. ; 14
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: The medial preoptic area (mPOA) participates in thermoregulatory control and blood pressure modulation as shown by studies with electrical stimulation of this area or cobalt chloride injection, a non-selective synapse inhibitor. This study aimed to investigate whether angiotensin II (Ang II) and GABA could act or not in the mPOA to mediate the cardiovascular and micturition control pathways. Methods: Female Wistar rats were submitted to stereotaxic surgery for implantation of a guide cannula into the mPOA 7days prior to the experiments. Afterwards, the animals were isoflurane- anesthetized and submitted to the catheterization of the femoral artery and vein and urinary bladder cannulation for mean arterial pressure (MAP), heart rate (HR), and intravesical pressure (IP) recordings, respectively. After the baseline MAP, HR, and IP recordings for 15min, Ang II (0.1nM, 1μL), losartan (AT-1 receptor antagonist, 100nM, 1μL), GABA (50mM, 1μL) or saline (1μL) were injected into the mPOA, and the variables were measured for additional 30min. In a different group of rats, the AT-1 receptor, angiotensin II converting enzyme (ACE), and GABAa receptor gene expression was evaluated in mPOA samples by qPCR. The data are as mean ± SEM and submitted to One-way ANOVA (Tukey posttest) or paired Student t-test (P <0.05). Results: The injection of Ang II into the mPOA evoked a significant hypotension (−37±10mmHg, n = 6, p = 0.024) and bradycardia (−47 ± 20bpm, p = 0.030) compared to saline (+1 ± 1mmHg and +6 ± 2bpm, n = 6). A significant increase in IP was observed after Ang II injection into the mPOA (+72.25 ± 17.91%, p = 0.015 vs. −1.80 ± 2.98%, n = 6, saline). No significant changes were observed in MAP, HR and IP after the losartan injection in the mPOA compared to saline injection. Injection of GABA into the mPOA evoked a significant fall in MAP and HR (−68 ± 2mmHg, n = 6, p < 0.0001 and −115 ± 14bpm, n = 6, p = 0.0002 vs. −1 ± 1mmHg and +4 ± 2bpm, n = 6, saline), but no significant changes were observed in IP. The AT-1 receptor, ACE and GABAa receptor mRNA expression was observed in all mPOA samples. Discussion: Therefore, in female rats, Ang II mediated transmission in the mPOA is involved in the cardiovascular regulation and in the control of central micturition pathways. A phasic control dependent on AT-1 receptors in the mPOA seems to be involved in the regulation of those cardiovascular and intravesical 3 parameters. In contrast, GABAergic transmission in the mPOA participates in the pathways of cardiovascular control in anesthetized female rats, nevertheless, this neurotransmission is not involved in the micturition control.
|
|
| 9. |
- Lamy, Gustavo B, et al.
(författare)
-
Lateral Preoptic Area Neurons Activated by Angiotensin-(1-7) Increase Intravesical Pressure: A Novel Feature in Central Micturition Control.
- 2021
-
Ingår i: Frontiers in physiology. - : Frontiers Media SA. - 1664-042X. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Central micturition control and urine storage involve a multisynaptic neuronal circuit for the efferent control of the urinary bladder. Electrical stimulation of the lateral preoptic area (LPA) at the level of the decussation of the anterior commissure in cats evokes relaxation of the bladder, whereas ventral stimulation of LPA evokes vigorous contraction. Endogenous Angiotensin-(1-7) [(Ang-(1-7)] synthesis depends on ACE-2, and its actions on binding to Mas receptors, which were found in LPA neurons. We aimed to investigate the Ang-(1-7) actions into the LPA on intravesical pressure (IP) and cardiovascular parameters. The gene and protein expressions of Mas receptors and ACE-2 were also evaluated in the LPA. Angiotensin-(1-7) (5 nmol/μL) or A-779 (Mas receptor antagonist, 50 nmol/μL) was injected into the LPA in anesthetized female Wistar rats; and the IP, mean arterial pressure (MAP), heart rate (HR), and renal conductance (RC) were recorded for 30 min. Unilateral injection of Ang-(1-7) into the LPA increased IP (187.46 ± 37.23%) with peak response at ∼23-25-min post-injection and yielded no changes in MAP, HR, and RC. Unilateral or bilateral injections of A-779 into the LPA decreased IP (-15.88 ± 2.76 and -27.30 ± 3.40%, respectively) and elicited no changes in MAP, HR, and RC. The genes and the protein expression of Mas receptors and ACE-2 were found in the LPA. Therefore, the LPA is an important part of the circuit involved in the urinary bladder control, in which the Ang-(1-7) synthetized into the LPA activates Mas receptors for increasing the IP independent on changes in RC and cardiovascular parameters.
|
|
| 10. |
- Lamy, Gustavo B, et al.
(författare)
-
Unveiling the Angiotensin-(1-7) Actions on the Urinary Bladder in Female Rats
- 2022
-
Ingår i: Frontiers in physiology. - : Frontiers Media SA. - 1664-042X. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Angiotensin-(1-7) is a peptide produced by different pathways, and regardless of the route, the angiotensin-converting enzyme 2 (ACE-2) is involved in one of the steps of its synthesis. Angiotensin-(1-7) binds to Mas receptors localized in different cells throughout the body. Whether angiotensin-(1-7) exerts any action in the urinary bladder (UB) is still unknown. We investigated the effects of intravenous and topical (in situ) administration of angiotensin-(1-7) on intravesical pressure (IP) and cardiovascular variables. In addition, the Mas receptors and ACE-2 gene and protein expression were analyzed in the UB. Adult female Wistar rats were anesthetized with 2% isoflurane in 100% O2 and submitted to the catheterization of the femoral artery and vein for mean arterial pressure (MAP) and heart rate (HR) recordings, and infusion of drugs, respectively. The renal blood flow was acquired using a Doppler flow probe placed around the left renal artery and the renal conductance (RC) was calculated as a ratio of Doppler shift (kHz) and MAP. The cannulation of the UB was performed for IP recording. We observed that angiotensin-(1-7) either administered intravenously [115.8 ± 28.6% angiotensin-(1-7) vs. -2.9 ± 1.3% saline] or topically [147.4 ± 18.9% angiotensin-(1-7) vs. 3.2 ± 2.8% saline] onto the UB evoked a significant (p < 0.05) increase in IP compared to saline and yielded no changes in MAP, HR, and RC. The marked response of angiotensin-(1-7) on the UB was also investigated using quantitative real-time polymerase chain reaction and western blotting assay, which demonstrated the mRNA and protein expression of Mas receptors in the bladder, respectively. ACE-2 mRNA and protein expression was also observed in the bladder. Therefore, the findings demonstrate that angiotensin-(1-7) acts in the UB to increase the IP and suggest that this peptide can be also locally synthesized in the UB.
|
|
