Angiotensin II, a stress-related neuropeptide in the CNS, facilitates micturition reflex in rats

We investigated the effects of centrally administered stress-related neuropeptide, angiotensin II, on the micturition reflex and the downstream signalling pathways in rats.

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 (AT₁ ) receptor antagonist], valsartan (an AT₁ receptor antagonist), PD123319 (an AT₂ 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.

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.

Angiotensin II in the CNS facilitates micturition reflex by inhibiting central GABAergic activity and activating the AT₁ receptor/PLC/PKC/NADPH oxidase/superoxide anion pathway.