Abstract

Central micturition control and urine storage involve a multisynaptic neuronal circuit for the efferent control of the urinary bladder. Electrical stimulation of the lateral preoptic area (LPA) at the level of the decussation of the anterior commissure in cats evokes relaxation of the bladder, whereas ventral stimulation of LPA evokes vigorous contraction. Endogenous Angiotensin-(1–7) [(Ang-(1–7)] synthesis depends on ACE-2, and its actions on binding to Mas receptors, which were found in LPA neurons. We aimed to investigate the Ang-(1–7) actions into the LPA on intravesical pressure (IP) and cardiovascular parameters. The gene and protein expressions of Mas receptors and ACE-2 were also evaluated in the LPA. Angiotensin-(1–7) (5 nmol/μL) or A-779 (Mas receptor antagonist, 50 nmol/μL) was injected into the LPA in anesthetized female Wistar rats; and the IP, mean arterial pressure (MAP), heart rate (HR), and renal conductance (RC) were recorded for 30 min. Unilateral injection of Ang-(1–7) into the LPA increased IP (187.46 ± 37.23%) with peak response at ∼23–25-min post-injection and yielded no changes in MAP, HR, and RC. Unilateral or bilateral injections of A-779 into the LPA decreased IP (−15.88 ± 2.76 and −27.30 ± 3.40%, respectively) and elicited no changes in MAP, HR, and RC. The genes and the protein expression of Mas receptors and ACE-2 were found in the LPA. Therefore, the LPA is an important part of the circuit involved in the urinary bladder control, in which the Ang-(1–7) synthetized into the LPA activates Mas receptors for increasing the IP independent on changes in RC and cardiovascular parameters.

Highlights

  • Urinary bladder dysfunctions can make the daily life activities difficult, causing social and mental discomfort

  • The unilateral injection of Ang- (1–7) into the lateral preoptic area (LPA) produced no significant changes in mean arterial pressure (MAP) (2 ± 2 mmHg), heart rate (HR) (–7 ± 7 bpm), and renal conductance (RC) (−2.23 ± 5.30%), a significant marked increase in intravesical pressure (IP) (187.46 ± 37.23%) was observed, both compared with baseline parameters and in comparison with saline injection into the LPA (p < 0.05) (Figures 3C, 4)

  • In contrast to Ang-(1–7) injections, we observed that the unilateral injection of A-779 into the LPA significantly decreased the intravesical pressure (−15.88 ± 2.76%), both compared with baseline and saline injections into the LPA (p < 0.05)

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Summary

Introduction

Urinary bladder dysfunctions can make the daily life activities difficult, causing social and mental discomfort. Among the urinary bladder dysfunctions, urinary incontinence symptoms have been reported with higher prevalence in women (Aoki et al, 2017). Central control of micturition and urine storage involves a complex and not fully understood mechanism. The maintenance of excretion and urinary storage depends on reflex mechanisms; this reflex arc can undergo direct cortical influence through facilitatory and inhibitory mechanisms. The onset of micturition is facilitated by the Pontine Micturition Center (PMC) (de Groat, 1998), while urinary storage is influenced by the Pontine Urine Storage Center (PUSC), which is located ventrolaterally in PMC

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