Aims: This study was initiated to investigate the involvement of neutrophil leukocyte activation in neurogenic inflammation, a process also involved in human urinary pathologies, elicited in the rat urinary bladder by the local administration of capsaicin, the archetypal TRPV1 agonist. The contribution of afferent nerves and sensory neuropeptides to leukocyte activation in the urinary bladder microcirculatory bed was examined. Methods: Following a 15-min topical application of capsaicin (50 μM), leukocyteendothelial interactions were examined for an observation period of 45 min with intravital microscopy. Expression of adhesion molecules E-selectin and ICAM-1 implicated in these interactions was assessed by immunohistochemistry. Selective sensory denervation was performed by neonatal treatment with capsaicin. The role of the TRPV1 receptor and two sensory neuropeptides (CGRP and substance P [SP]) were studied using the selective antagonists capsazepine, CGRP 8-37 and RP67580, respectively. Results: Capsaicin induced rapid increases in leukocyte rolling and adhesion and increased the expression of E-selectin and ICAM-1 in the postcapillary venules.Sensory chemodenervation via capsaicin and also TRPV1 receptor antagonism effectively prevented these changes. A similar reduction was observed in leukocyte adhesion after topical application of CGRP 8-34 or RP67580, but only CGRP reduced the capsaicin-evoked leukocyte rolling. Conclusions: Topical application of capsaicin induces early neurogenically mediated cellular microcirculatory inflammatory reactions via the activation of the TRPV1 receptor and the release of CGRP and SP from sensory nerves in the bladder.Co-administration of SP and CGRP receptor antagonists may ameliorate microcirculatory inflammatory changes elicited by capsaicin in the urinary bladder.

Összefoglaló. Az alsó húgyutak fő funkciója a vizelet tárolása és ürítése, amely működések zavara az úgynevezett alsó húgyúti tünetegyüttes kialakulásához vezet, ami a kiváltó októl függően vizeletürítési zavarral és vizeletretencióval is járhat. Kezeletlen esetekben a felső húgyutak károsodása következik be a magas hólyagnyomás által kiváltott vesicoureteralis reflux következtében, amely ureter- és veseüregrendszeri tágulat kialakulására, illetve fertőzésekre és kőképződésre hajlamosít. A vizelettárolási/vizeletürítési zavarokat három fő csoportba sorolhatjuk, úgymint stressz- (terheléses) inkontinencia , hiperaktív hólyag (nedves/száraz) és neurogén hólyag. A jelen összefoglaló közlemény tárgyát képező neurogén hólyag egy gyűjtőfogalom, mely magában foglal minden, releváns neurológiai kórkép talaján kialakult vizelettárolási és vizeletürítési zavart. Mivel a húgyhólyag mellett a záróizomzat és a hátsó húgycső is érintett, ezt a kórképet napjainkban „neurogén alsó húgyúti diszfunkció” elnevezéssel is szokás illetni. A kórállapotot a neurológiai diszfunkciók széles spektruma okozhatja, kezdve a helyi funkcionális zavartól a helyi idegi sérülésen át a felső és alsó motoneuron-sérülésig vagy a centrális degeneratív folyamatokig. Az eltérő etiológia ellenére a klinikai tünetek rendszerint két alapvető klinikai típusban manifesztálódhatnak: túlműködő (fokozott detrusorkontraktilitást okozó automata) hólyag vagy alulműködő hólyag formájában. Tekintettel a neurogén alsó húgyúti diszfunkció következtében létrejövő felső húgyúti komplikációkra, a közlemény egyik célja a betegség diagnózisát segítő algoritmus bemutatása a legújabb nemzetközi szakirodalmi ismeretek alapján. A neurogén hólyag kezelése jobbára nem terjedhet ki a kiváltó ok kezelésére, ezért a jelen összefoglaló másik célja azon gyógyszeres és invazív terápiás beavatkozások összefoglalása, melyek a felső húgyutak védelmét szolgálják az alacsony hólyagnyomás fenntartása révén. Orv Hetil. 2021; 162(4): 135–143. Summary. Storage and urination are the main functions of the lower urinary tract and its lesions lead to the so-called lower urinary tract syndrome causing either urinary incontinence or retention. In untreated cases, the upper urinary tract becomes injured via a vesicoureteral reflux resulting from increased bladder pressure and resultant dilations of the ureter and the renal pelvis which predispose to infection and stone formation. Lower urinary tract storage/urination disorders can be classified as stress incontinence, hyperactive bladder (wet/dry) and neurogenic bladder. Neurogenic bladder which is the subject of this review, is a collective term that encompasses all urinary storage and emptying disorders which develop on the basis of neurological diseases. Being not only the bladder, but also the sphincter and posterior urethra (generally termed as the “bladder outlet”) affected, nowadays this condition is referred to as “neurogenic lower urinary tract dysfunction”. A wide range of neurological dysfunctions could contribute to the development of this condition, ranging from local dysfunction (autonomic dysreflexia) or local nerve injury to upper/lower motoneuron injury or central degenerative processes. Regardless of the diverse etiology, the clinical symptoms eventually manifest in two major forms, i.e., overacting (automatic bladder with increased detrusor contractility) and underactive bladder. Considering the severity of complication occurring in the upper urinary tract in response to the pathophysiological changes in the lower urinary tract, one of the aims of this paper was to present an algorithm aiming to build up a state of the art diagnosis of the disease based on current international literature data. Since treatment of the neurogenic bladder usually can not target elimination of the underlying cause, the other goal of the present paper is to summarize the pharmacological treatment regimen and invasive therapeutic interventions that protect the upper urinary tract by maintaining low pressure values in the bladder. Orv Hetil. 2021; 162(4): 135–143.

One-hundred forty-five students volunteered to test the effects of salt and water loading on kidney function. Students were investigated beginning at 8:40 a.m., 1:40 p.m., and 6:40 p.m. They were approximately evenly distributed between male and female genders and were of multiple cultural/ethnic backgrounds. Upon entering the laboratory baseline data were collected. Approximately half of the volunteers then consumed 200 mL of a 2.0% NaCl solution (n=77). The others directly consumed 1.0 L of tap water (n=68). Upon entering the laboratory baseline data were collected. The others directly consumed 1.0 L of tap water. Kidney function was monitored each 30 minutes for the next 90 minutes. Under baseline conditions, urine osmolality was elevated in all students (≥ 280 mOsm/kg) but was significantly (P<0.05) greater in the 8:40 a.m. group than in either of the p.m. groups. Urine specific gravity and sodium excretion were also elevated in the 8:40 a.m. group compared to the others. Urine flow rate was least in the 8:40 group and greatest in the 1:40 p.m. group. We conclude that in these students renal function was influenced by a diurnal pattern. We also conclude that without compelling incentives (e.g. financial, gradeinfluencing) it was virtually impossible to get students to comply with pre-experimental instructions (e.g. no salt-laden meals after 6:00 p.m. before the day of experimentation).

Our results demonstrate that direct endothelial injury (caused by IR), as well as protamine sulphate and cyclophosphamide administrations induce inflammatory microcirculatory changes of the urinary bladder. These observations suggest a causative role for microcirculatory disturbances in the pathogenesis of interstitial cystitis and hemorrhagic cystitis as well.

The microcirculatory aspects of inflammatory disorders are of importance in the pathology of the urinary system. Our first aim was to perform a comparative analysis of the microcirculatory responses of the urinary bladder in infectious and non-infectious inflammatory animal models with direct or indirect endothelial damage. To this end, we compared the local microcirculatory consequences of experimental interstitial (IC) cystitis and hemorrhagic cystitis (HC) with those of bladder ischemia/reperfusion (IR). We found that not only IR, where direct endothelial damage is present, but also HC and IC, where microcirculatory inflammatory reactions are secondary after urothelial and interstitial damage, are associated with manifest polymorphonuclear leukocyte (PMN)–endothelial cell interactions. This finding confirms the common role of PMN-mediated microcirculatory reactions in the pathogenesis of bladder diseases. The overexpression of transient receptor potential vanilloid type 1 (TRPV1) has been demonstrated in IC cases as well as in cases of neurogenic bladder. In addition, TRPV1 agonists have also previously been used during pharmacological management of these diseases. Therefore, our next aim was to examine the microcirculatory effects of local capsaicin treatment (the archetypical TRPV1 agonist). In our study, capsaicin induced rapid increases in PMN leukocyte rolling and adhesion and in adhesion molecule expression in the postcapillary venules of the urinary bladder, which was prevented by neonatal sensory chemodenervation with capsaicin and competitive TRPV1 antagonism. The effect of specific receptor antagonist therapy showed that TRPV1-induced calcitonin gene-related peptide (CGRP) release initiates the PMN–endothelial cell interaction by promoting leukocyte rolling, but adhesion is influenced by both CGRP and substance P. Our final goal is to implement medical research in clinical practice. Depending on the underlying cause, neurogenic bladder can manifest in both overactive and underactive forms. Diagnosis and treatment of both manifestations of neurogenic bladder remain a challenge in urology practice because disease severity cannot easily be assessed and the most common symptoms are non-specific. For this reason, our last aim was to provide an algorithm that aims to facilitate rapid and efficient diagnosis and assessment of disease severity. This may also aid in decision making on the potential pharmacological and invasive therapeutic approaches to protecting the upper urinary tract by maintaining low pressure values in the bladder.