Adriana Zapparoli

Impaired dipsogenic and renal response to repetitive intracerebroventricular angiotensin II (AngII) injections in rats

The role of the central nervous system (CNS) in the control of blood pressure and hydrosaline homeostasis has been demonstrated by several studies. While circulating angiotensin II (AngII) tends to retain sodium by a direct renal action as well as through aldosterone release, stimulation of brain AngII receptors has been reported to induce natriuresis. Repetitive intracerebroventricular AngII injection was recently demonstrated to be capable of leading to desensitisation of the dipsogenic effect of AngII stimuli. The aim of the current study was to investigate a possible central desensitisation to AngII stimuli by observing the effects of a low-concentration solution of AngII on the dipsogenic and natriuretic mechanisms in conscious rats, compared with appropriate age-matched 0.15 M NaCl-injected subjects, as evaluated by lithium clearance. The present report confirmed earlier reports on the potent natriuretic and dipsogenic effects of central AngII receptor stimulation. Natriuresis is mediated by a decrease in sodium reabsorption in the proximal and post-proximal tubule segments of the nephron. The current findings lend further support to the idea that AngII, in the CNS, is instrumental in the regulation of body fluid homeostasis. The magnitude of the dipsogenic and renal response to AngII was significantly decreased by repetitive stimulus.

Hypothalamic SOCS-3 expression and the effect of intracerebroventricular angiotensin II injection on water intake and renal sodium handling in SHR

In rats, the acute central dipsogenic and natriuretic action of angiotensin II (AngII) seems to be independent of the hemodynamic effects of the peptide; however, in genetically hypertensive models, this relationship has not yet been investigated. It has been demonstrated that AngII induces the suppressor of cytokine signaling (SOCS-3) expression in the brain that, in turn, modulates further activation of the pathway, leading to desensitization to AngII stimuli with regard to its dipsogenic effect. This study investigates age-related Janus kinase (JAK-2) and SOCS-3 hypothalamic expression, by immunoblotting, and the involvement of SOCS-3 expression in urinary sodium handling and dipsogenic response in spontaneously hypertensive rats (SHR), compared with age-matched Wistar–Kyoto (WKy) rats. The intracerebroventricular (i.c.v.) application of AngII significantly enhanced the dipsogenic response, reduced CCr, and reciprocally promoted increased absolute and fractional rates of excretion of sodium in WKy rats. The central AngII-induced dipsogenic effect in WKy and SHR was significantly attenuated by prior i.c.v. administration of DUP753. In addition, the magnitude of the dipsogenic and renal response to AngII was significantly attenuated in age-matched SHR. Blocking of hypothalamic SOCS-3 expression by an antisense oligonucleotide resulted in partial reversal of the refractory nature of AngII in thirst responses in SHR. The altered centrally applied AngII response in SHR associated with increased hypothalamic JAK-2/SOCS-3 expression may suggest that abnormal regulation of the central angiotensin pathways may contribute to dysfunction of water–electrolyte homeostasis in SHR.

Menthol ameliorates voiding dysfunction in types I and II diabetic mouse model

Overactive bladder (OAB) is one of the most common complications of both type 1 (T1DM) and type 2 diabetes mellitus (T2DM). In healthy conditions, menthol infused intravesically reduces the threshold for initiating micturition reflex, but no study evaluated its effects in diabetic conditions. Therefore, we have used mouse models of T1DM and T2DM to evaluate the effects of menthol on cystometric alterations and increased bladder contractility in vitro.