Drug therapy targeting angiotensin II type 1 receptors in the brain against frequent urination

Abstract

The production of angiotensin II (Ang II) in the brain plays important roles as neurotransmitter and neuropeptide. Central Ang II is involved in regulating various physiological processes, such as blood pressure and water homeostasis, via Ang II type 1 (AT1) receptors. We have demonstrated that Ang II induces frequent urination via AT1 receptors in the brain even at doses that does not seem to affect the blood pressure in animal experiment. Intracerebroventricular administration of Ang II was also found to reduce the bladder capacity without affecting the maximum voiding pressure, post voiding residual urine volume or voiding efficiency. Additionally, the activation of AT1 receptor downstream signal pathway (phospholipase C/protein kinase C/NADPH oxidase/superoxide anion) and suppression of GABAergic nervous system in the brain are involved in the mechanism underlying the central Ang II-inducted frequent urination. AT1 receptor antagonists have been widely used to treat hypertension. We demonstrated that peripherally administered AT1 receptor antagonist telmisartan, which can penetrate blood brain barrier, exerted an inhibitory effect on central Ang II-inducted frequent urination. At this symposium, we would present and discuss the possible drug therapy targeting AT1 receptors in the brain against frequent urination on the results obtained from our recent research work.