Angiotensin II, a stress-related neuropeptide in the central nervous system facilitates micturition reflex in rats.

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 (30pmol). Muscimol (a GABA(A) receptor agonist) or baclofen (a GABA(B) receptor agonist) was i.c.v. administered 30min before or 15min 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 30min 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.