We examined the effects of losartan, an angiotensin II type 1 receptor blocker, on prostatic hyperplasia in spontaneously hypertensive rats (SHRs). Thirty-six-old male SHRs were perorally treated with losartan (3 or 10 mg/kg) or vehicle once daily for 18 weeks. Wistar Kyoto rats (WKYs) were used as vehicle-treated controls. After the treatment, prostate weight, blood pressure, and prostatic blood flow were measured. The tissue malondialdehyde (MDA), interleukin-6 (IL-6), and basic fibroblast growth factor (bFGF) levels were measured. Histological analysis for the ventral prostate was performed by hematoxylin and eosin staining. Compared to the WKYs, the SHRs had significantly higher prostate weight, prostate weight/body weight ratio (PBR), blood pressure, glandular epithelial area, and tissue MDA, IL-6 and bFGF levels in the ventral prostate and lower prostatic blood flow. Treatment with losartan dose dependently caused recovery of prostatic blood flow and decreased PBR, blood pressure, glandular epithelial area, and tissue MDA, IL-6, and bFGF levels in SHRs. Chronic losartan treatment could improve the prostatic hyperplasia via recovery of reduction in prostatic blood flow in ventral prostate in SHRs.
We investigated the possible mechanism which central angiotensin II (Ang II) facilitates micturition reflex focusing on the Ang II type 1 receptor (AT1R), GABAR or corticotropin-releasing factor (CRF)R. And, we examined whether a centrally acting AT1R antagonist telmisartan (TEL) ameliorates the central Ang II induced stimulation of micturition reflex. Materials and Methods: Male Wistar rats were anesthetized with urethane, and cystomety was performed. TEL, GABA A R agonist (muscimol: Mus), GABA B R agonist (baclofen: Bac) or CRF1R antagonist (CP154526: CP) was icv administered before icv Ang II administration in the rats. Some rats were perorally administered with TEL (10 mg/kg/day) or no centrally acting AT1R antagonist (valsartan: Val, 10 mg/kg) for 8 days. Then, Ang II was icv administered in the rats. Results: TEL, Mus, Bac or CP significantly suppressed Ang II induced shortening of intercontraction interval (ICI). Chronic pre-treatment with TEL but not Val inhibited the Ang II induced shortening of ICI. Conclusion: Central Ang II can facilitate the micturition reflex via modulating the AT1R, GABAR or CRF1R. Blocking of the central AT1R might be a therapeutic target for treatment of detrusor overactivity.
INTRODUCTION AND OBJECTIVES: Bioelectronic technologies that are capable of modulating activity of the peripheral nervous system offer powerful options in targeted treatment of organ dysfunction and pain, with features that have the potential to bypass limitations of traditional pharmacological approaches. Here we introduce a miniaturized, fully implantable wireless bio-optoelectronic system that circumvents these challenges by monitoring and modulating bladder function in an active, closed-loop fashion through optogenetic, as opposed to electrical, modulation of bladder-projecting sensory afferents.METHODS: The resulting technology includes a wireless strain gauge that wraps around the bladder, enabling measurement of changes bladder size, and includes integrated microscale light emitting diodes (µLEDs) to allow optogenetic modulation. This approach avoids the use of potentially damaging nerve-interfacing electrodes or implantation of invasive bladder catheters, which can disrupt normal bladder function. The strain gauge and mLEDs operate via an implanted Bluetooth base station that allows for wireless monitoring of bladder activity and enables closed-loop control via optogenetics. Utilizing herpes simplex viral (HSV) vectors to deliver the lightactivated proton pump, archaerhodopsin (Arch, which can inhibit neuronal firing) to bladder afferents.RESULTS: We can chronically measure bladder activity using the implanted strain gauge and these measurements correlate with traditional bladder pressure cystometry, void volumes and overall bladder size. Using the wireless optoelectronic strain gauge, we can clearly identify the onset of altered voiding behaviors associated with bladder inflammation, and activation of Arch in bladder afferents can reduce the number of void associated with inflammation. We programed our software to recognize these changes in bladder frequency associated with bladder inflammation and to activate the µLEDs. Closed loop activation of µLEDs reduced voiding frequency in the Arch-injected animal compared to eYFP.CONCLUSIONS: These advances will enable novel insight into the mechanisms of bladder control and pain as well as lay the groundwork for potential optogenetic and closed loop interventions to treat other visceral diseases.
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