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Angiotensin II, a stress‐related neuropeptide in the CNS, facilitates micturition reflex in rats
Author(s) -
Shimizu Shogo,
Shimizu Takahiro,
Nakamura Kumiko,
Higashi Youichirou,
Saito Motoaki
Publication year - 2018
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.14439
Subject(s) - angiotensin ii , apocynin , endocrinology , pharmacology , medicine , angiotensin receptor , chemistry , agonist , valsartan , muscimol , nadph oxidase , receptor , oxidative stress , blood pressure
Background and Purpose We investigated the effects of centrally administered stress‐related neuropeptide, angiotensin II, on the micturition reflex and the downstream signalling pathways in rats. Experimental Approach Male Wistar rats were anaesthetized with urethane for cystometry before and after i.c.v. administration of vehicle or angiotensin II (30 pmol). Muscimol (a GABA A receptor agonist) or baclofen (a GABA B receptor agonist) was i.c.v. administered 30 min before or 15 min after central angiotensin II administration. Telmisartan [an angiotensin II type 1 (AT 1 ) receptor antagonist], valsartan (an AT 1 receptor antagonist), PD123319 (an AT 2 receptor antagonist), U‐73122 (a PLC inhibitor), chelerythrine chloride (a PKC inhibitor), apocynin (a NADPH oxidase inhibitor) or tempol (an antioxidant) was centrally administered 30 min before central angiotensin II administration. Key Results Centrally administered angiotensin II significantly shortened the intercontraction interval and decreased the voided volume and bladder capacity without altering the maximum voiding pressure, post‐voiding residual urine volume or voiding efficacy. Muscimol, baclofen, telmisartan, valsartan, U‐73122, chelerythrine chloride, apocynin or tempol pretreatment significantly suppressed the reduction in intercontraction interval induced by central angiotensin II. Post‐treatment with muscimol or baclofen also ameliorated the decrease in intercontraction interval induced by central angiotensin II. Conclusions and Implications Angiotensin II in the CNS facilitates micturition reflex by inhibiting central GABAergic activity and activating the AT 1 receptor/PLC/PKC/NADPH oxidase/superoxide anion pathway.