Central angiotensin II type 1 receptors as a possible target for treatment of detrusor overactivity

Abstract

Purpose: 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_AR agonist (muscimol: Mus), GABA_BR 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.