Central angiotensin II type 1 receptor as a therapeutic target against frequent urination

Abstract

Aims The goal of this study was to test whether central corticotropin‐releasing factor (CRF) was involved in angiotensin II (Ang II) and Ang II type 1 (AT1) receptor‐mediated facilitation of micturition reflex and to investigate whether peripherally administered telmisartan, AT1 receptor antagonist, suppresses the central Ang II‐induced facilitation of micturition reflex in rats. Methods Urethane anesthetized male Wistar rats were placed under continuous cystometry before and after intracerebroventricular administration of each drug. Rats were intracerebroventricularly administered telmisartan (AT1 receptor antagonist), CP154526 (CRF1 receptor antagonist), or K41498 (CRF2 receptor antagonist) 30 minutes before intracerebroventricular administration of Ang II. Some male Wistar rats were perorally pretreated with either vehicle, AT1 receptor antagonist telmisartan or valsartan, once daily for 8 days, then measured blood pressure. Thereafter, Ang II was intracerebroventricularly administered for continuous cystometry. Results Intracerebroventricularly administered telmisartan or CP154526 dose‐dependently suppressed the central Ang II‐induced intercontraction interval (ICI) reduction. In contrast, intracerebroventricularly administered K41498 did not affect the central Ang II‐induced response compared to vehicle pretreatment. Peripherally administered telmisartan but not valsartan suppressed the central Ang II‐induced ICI reduction in rats compared to vehicle administration without altering blood pressure. Conclusions Central Ang II induced facilitation of the micturition reflex through AT1 and CRF1 receptors. Peripherally administered telmisartan suppressed central Ang II‐induced facilitation of micturition reflex.

Psychological/mental stress‐induced effects on urinary function: Possible brain molecules related to psychological/mental stress‐induced effects on urinary function

“…Therefore, similar to BB, we examined the effects of centrally administered AngII on micturition in relation to the sympatho‐adrenomedullary outflow. In our studies, centrally administered AngII induced ICI shortening, and reductions in BC and SVV without changing RV, and the AngII‐induced ICI shortening was not influenced by ADX in rats 110–112 . In addition, the AngII‐induced ICI shortening was suppressed by central pretreatment with valsartan and telmisartan (AT1 receptor antagonists), but not PD123319 (AT2 receptor antagonist), in rats 110–112 .…”

“…In our studies, centrally administered AngII induced ICI shortening, and reductions in BC and SVV without changing RV, and the AngII-induced ICI shortening was not influenced by ADX in rats. [110][111][112] In addition, the AngII-induced ICI shortening was suppressed by central pretreatment with valsartan and telmisartan (AT1 receptor antagonists), but not PD123319 (AT2 receptor antagonist), in rats. [110][111][112] These data show that brain AngII can induce frequent urination through brain AT1 receptors, independently of the sympathoadrenomedullary outflow, a representative stress response.…”

“…[110][111][112] In addition, the AngII-induced ICI shortening was suppressed by central pretreatment with valsartan and telmisartan (AT1 receptor antagonists), but not PD123319 (AT2 receptor antagonist), in rats. [110][111][112] These data show that brain AngII can induce frequent urination through brain AT1 receptors, independently of the sympathoadrenomedullary outflow, a representative stress response. AngII in the brain is reported to inhibit GABAergic synaptic transmission.…”