Lateral Preoptic Area Neurons Activated by Angiotensin-(1–7) Increase Intravesical Pressure: A Novel Feature in Central Micturition Control

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.

Unveiling the Angiotensin-(1–7) Actions on the Urinary Bladder in Female Rats

“…On the other hand, another hypothesis is that Ang-(1–7) infused intravenously could also act centrally in the lateral preoptic area and bind to the Mas receptors of this area. Previous report has shown that Ang-(1–7) injected into the lateral preoptic area increases IP with a latency for the response of approximately 10 min and achieves a peak response approximately 25 min after injection without inducing any changes in RC and arterial pressure ( Lamy et al, 2021 ). Hence, the response observed with Ang-(1–7) infused intravenously in the current study could be dependent on direct action on the UB and/or be due to an action at the intrarenal level and/or through activation of Mas receptors in the lateral preoptic area.…”

“…The Image Lab software TM (Bio-rad) was used to quantify the densitometry of the blot containing the corresponding protein of interest. The optical density (OD) of Mas receptors and ACE-2 was normalized by the expression of total protein, as described in a previous study by Lamy et al (2021) .…”

“…A small incision was carried out in the apex of the UB wall for insertion of a polyethylene tubing (PE-50 connected to PE-10, Clay Adams, NJ, United States) filled with saline as previously described by Cafarchio et al (2016Cafarchio et al ( , 2018Cafarchio et al ( , and 2020, Magaldi et al (2020), andLamy et al (2021). Tissue glue was used to keep the catheter fixed on the bladder wall for intravesical pressure (IP) recordings in a data acquisition system (PowerLab 16 SP, AD Instruments, Castle Hill, AU).…”

“…Previous studies in Mas-knockout mice have demonstrated cardiovascular changes, ranging from induced hypertension and structural alterations in blood vessels to metabolic problems (Santos et al, 2006) (Xu et al, 2008), (de Moura et al, 2010) (Xu et al, 2008) (Santos et al, 2006). Lamy et al (2021) have demonstrated that Ang-(1-7) synthesized locally in the lateral preoptic area activates Mas receptors, which increases the IP without changes in renal conductance (RC) and cardiovascular variables. Despite Ang-(1-7) being found both peripherally and centrally (Santos and Campagnole-Santos, 1994), the role of Ang-(1-7) in the peripheral mechanisms involved in UB control is, to the best of our knowledge, largely unknown.…”

“… Lamy et al (2021) have demonstrated that Ang-(1–7) synthesized locally in the lateral preoptic area activates Mas receptors, which increases the IP without changes in renal conductance (RC) and cardiovascular variables. Despite Ang-(1–7) being found both peripherally and centrally ( Santos and Campagnole-Santos, 1994 ), the role of Ang-(1–7) in the peripheral mechanisms involved in UB control is, to the best of our knowledge, largely unknown.…”