<b>Naftopidil improves locomotor activity and urinary frequency in rats with pelvic venous </b><b>congestion </b>

Abstract

The α1D/A receptor antagonist, naftopidil, inhibits micturition reflex by acting on various different sites. We examined the effects of naftopidil on bladder activity and changes in the induced urinary frequency using female rats with pelvic venous congestion (PC). Twenty-four female rats were divided into sham, PC, and PC/naftopidil groups. After anesthetizing rats in the PC and PC/naftopidil groups, the bilateral common iliac veins and uterine veins were ligated. Rats in the sham and PC groups were fed a standard diet, while rats in the PC/naftopidil group were fed diets containing 0.04% naftopidil. After 4 weeks of treatment, locomotor activity, urinary nitric oxide metabolites (NOx), continuous cystometry, and plasma monoamine measurements were performed. PC rats exhibited a decrease of locomotor activity, a shorter interval between bladder contractions on continuous cystometry, and decreased urinary NOx and plasma serotonin levels than the sham rats. The PC/naftopidil rats exhibited an increase of locomotor activity, a longer interval between bladder contractions, and increased urinary NOx and plasma serotonin levels. Therefore, naftopidil might improve bladder dysfunction induced by pelvic venous congestion due to several actions in the central nervous system and bladder tissue, as well as acting as an α1 blocker to cause pelvic venous dilation.Unilateral or bilateral ovarian vein incompetence can cause pelvic congestion syndrome, which induces chronic pain, irritable bladder, dysfunction of the pelvic organs, or vulval varices and varicose veins in the lower limbs (1, 5, 7). Our previous study demonstrated that chronic prostatitis and stress urinary incontinence were related to the existence of vena cava reflux caused by tricuspid regurgitation (28). When we examined a female case with pelvic congestion syndrome using external iliac venography, we found that pelvic venous congestion occurred with tricuspid regurgitation and without pelvic venous valves (25). Our previous studies have also demonstrated that ligation of the bilateral common iliac veins in male rats or ligation of the bilateral common iliac veins and uterine veins in female rats induced changes in the urinary frequency and low locomotor activity (30). As compared to the intact rats, these surgically altered rats exhibited a bladder blood flow decrease that was about 80% of the flow in the intact bladder. Therefore, pelvic venous congestion may be one of the causes of pelvic ischemia, and might be related to several lower urinary tract symptoms/diseases. When examining hypertension, the relevance of lower urinary tract symptoms and their association with hypertension need to be taken into consideration. Spontaneously hypertensive rats have been shown to have a significantly lower bladder capacity and voiding volume (24), and these rats also exhibit

Mechanisms underlying the effects of propiverine on bladder activity in rats with pelvic venous congestion and urinary frequency

“…Administration of propiverine also led to an increase in locomotor activity to the level in the sham group, and urinary NOx was increased to the sham level. These effects of propiverine were similar to those noted in our previous studies of silodosin (an adrenergic alpha-1A antagonist) (13) and naftopidil (an adrenergic alpha-1D/A antagonist) in rats with pelvic venous congestion (14). However, propiverine decreased the urinary level of 8-OHdG, a marker of oxidative stress, to below that in the sham group, although silodosin tion, as demonstrated by the decrease in urinary 8-OHdG, decrease in iNOS mRNA expression, increase in total NOx due to nNOS activation, and downregulation of M3 and TRPV1 receptor expression.…”

“…Assessment of locomotor activity. After assessment of voiding behaviour, locomotor activity was investigated as a surrogate marker of pelvic pain (14). Rats were housed individually in plastic cages with increasing the single voided volume.…”

“…When we performed external iliac venography in a woman with pelvic congestion syndrome, we found that pelvic venous congestion was associated with tricuspid regurgitation and absence of pelvic venous valves (11). Our previous studies have also demonstrated that ligation of the bilateral common iliac veins in male rats or ligation of the bilateral common iliac veins and uterine veins in female rats induces changes of urinary frequency and locomotor activity (12)(13)(14)(15). In these rat models of venous ligation, bladder blood flow is decreased by about 80% compared with that in intact rats (15).…”

<b>Pelvic venous congestion induces lower urinary tract dysfunction in </b><b>rats </b>

“…To create a pelvic venous congestion (PC) model, 8 or 9 weeks old female Sprague-Dawley rats were anesthetized with 2% isoflurane. After an incision was made in the lower abdomen, the bilateral common iliac veins were ligated with metal clips, and the bilateral uterine veins with uterine arteries and uterine horn were ligated en bloc at a site near the ovaries (32). The distal common iliac veins became dilated after ligation of these veins.…”

In Vitro Effects of Plasma Collected From Rats Administered Naftopidil on Whole Urinary Bladder Preparation Isolated From Rats

“…Naftopidil, one such α1-adrenoceptor blocker, appears to counter voiding symptoms by reducing urethral tonus [10]. This compound's activity against storage symptoms has been determined in several studies, as follows: (1) decreasing urine adenosine 5'-triphosphate levels [11], (2) regulating afferent C-fiber or spinal glycine and/or γ-amino butyric acid receptor activity [12,13], and (3) potentiating blood flow in the urinary bladder [4] while also altering the level of urine nitric oxide (NO) metabolites [14]. However, it is still unknown whether naftopidil acts directly in the urinary bladder.…”