Localization of IP in rabbit kidney and functional role of the PGI(2)/IP system in cortical collecting duct.
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To clarify the role of the PGI(2)/PGI(2) receptor (IP) system in rabbit cortical collecting duct (RCCD), we characterized the expression of IP receptors in the rabbit kidney. We show by Northern and Western blotting that IP mRNA and protein was detectable in all three regions of the kidney. To determine how PGI(2) signals, we compared the effects of different PGI(2) analogs [iloprost (ILP), carba-prostacyclin (c-PGI(2)), and cicaprost (CCP)] in the isolated perfused RCCD. PGI(2) analogs did not increase water flow (L(p)). Although PGI(2) analogs did not reduce an established L(p) response to 8-chlorophenylthio-cAMP, they equipotently inhibited AVP-stimulated L(p) by 45%. The inhibitory effect of ILP and c-PGI(2) on AVP-stimulated L(p) is partially reversed by the protein kinase C inhibitor staurosporine and abolished by pertussis toxin; no effect was obtained with CCP. In fura 2-loaded RCCD, CCP did not alter cytosolic Ca(2+) concentration ([Ca(2+)](i)), but, in the presence of CCP, individual infusion of ILP and PGE(2) increased [Ca(2+)](i), suggesting that CCP did not cause desensitization to either ILP or PGE(2). We concluded that ILP and c-PGI(2) activate PKC and the liberation of [Ca(2+)](i) but not CCP. This suggested an important role for phosphatidylinositol hydrolysis in mediating ILP and c-PGI(2) effects but not CCP in RCCD. (+info)
Outcomes after total versus subtotal abdominal hysterectomy.
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BACKGROUND: It is uncertain whether subtotal abdominal hysterectomy results in better bladder, bowel, or sexual function than total abdominal hysterectomy. METHODS: We conducted a randomized, double-blind trial comparing total and subtotal abdominal hysterectomy in 279 women referred for hysterectomy because of benign disease; most of the women were premenopausal. The main outcomes were measures of bladder, bowel, and sexual function at 12 months. We also evaluated postoperative complications. RESULTS: The rates of urinary frequency (urination more than seven times during the day) were 33 percent in the subtotal-hysterectomy group and 31 percent in the total-hysterectomy group before surgery, and they fell to 24 percent and 20 percent, respectively, at 12 months (P=0.03 for the change over time within each group; P=0.84 for the interaction between the treatment assignment and time). The reduction in nocturia and stress incontinence and the improvement in bladder capacity were similar in the two groups. The frequency of bowel symptoms (as indicated by reported constipation and use of laxatives) and measures of sexual function (including the frequency of intercourse and orgasm and the rating of the sexual relationship with a partner) did not change significantly in either group after surgery. The women in the subtotal-hysterectomy group had a shorter hospital stay (5.2 days, vs. 6.0 in the total-hysterectomy group; P=0.04) and a lower rate of fever (6 percent vs. 19 percent, P<0.001). After subtotal abdominal hysterectomy, 7 percent of women had cyclical bleeding and 2 percent had cervical prolapse. CONCLUSIONS: Neither subtotal nor total abdominal hysterectomy adversely affects pelvic organ function at 12 months. Subtotal abdominal hysterectomy results in more rapid recovery and fewer short-term complications but infrequently causes cyclical bleeding or cervical prolapse. (+info)
Discrimination of bladder disorders in female lower urinary tract symptoms on ultrasonographic cystourethrography.
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OBJECTIVE: To evaluate morphologic features of bladder disorders in female lower urinary tract symptoms using ultrasonographic cystourethrography and to elucidate the anatomic association of these morphologic characteristics. METHODS: Ultrasonographic cystourethrography was performed in 1049 women with lower urinary tract symptoms and 1 single urodynamic diagnosis, including 764 patients with genuine stress incontinence, 190 with detrusor instability, and 95 with a hypersensitive bladder. Thirty-six women with no lower urinary tract symptoms served as control subjects. Ultrasonographic assessment included measurement of the bladder neck position at rest and during stress and observation of the development of bladder neck funneling and cystocele during the Valsalva maneuver. RESULTS: Hypersensitive bladder and control groups had a significantly higher bladder neck position at rest and during stress, a lesser rotational angle of the bladder neck, a lower prevalence of bladder neck funneling and cystocele formation, and lesser mean bladder wall thickness than the other diagnostic groups. In the study groups, age, parity, and menopause may have effects on the cystourethrographic parameters except rotational angle and funneling of the bladder neck. With control of the confounding factors, bladder wall thickness at the trigone and dome was negatively correlated with the resting bladder neck angle (P = .006 and 0.019, respectively). Bladder wall thickness at the dome was positively associated with the rotational angle of the bladder neck (P = .022). Funneling of the bladder neck and development of cystocele during stress were positively associated with the resting and straining bladder neck angles as well as the rotational angle of the bladder neck. CONCLUSIONS: Ultrasonographic manifestation of a hypersensitive bladder is significantly different from that of genuine stress incontinence and detrusor instability. (+info)
The effect of chloroquine on renal function and vasopressin secretion: a nitric oxide-dependent effect.
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We have previously reported that chloroquine administration increases plasma vasopressin concentration and urinary sodium excretion in Sprague-Dawley rats. Because chloroquine has also been shown to stimulate nitric oxide production, the aim of this study was to determine whether nitric oxide mediates chloroquine-induced changes in renal function and secretion of vasopressin. Sprague-Dawley rats (n = 6-8/group) were infused with 2.5% dextrose under Intraval anesthesia (100 mg kg(-1) i.p.). After 3-h equilibration and a control hour, animals received either vehicle, chloroquine (0.04 mg h(-1)), N(omega)-nitro-L-arginine methyl ester (L-NAME) (nitric-oxide synthase inhibitor, 60 microg kg(-1) h(-1)), or combined chloroquine and L-NAME over the next hour. L-NAME or vehicle infusion continued for a further recovery hour. Plasma was collected from a parallel group of animals for vasopressin radioimmunoassay. Chloroquine stimulated a significant increase (p < 0.05) in urine flow rate, glomerular filtration rate, and sodium excretion over the hour of infusion, in comparison with vehicle-infused rats. These effects continued after cessation of chloroquine, reaching maxima in the following recovery hour. Coadministration of L-NAME abolished these effects, returning all parameters to levels comparable with those in vehicle-infused animals. Chloroquine administration was accompanied by a significant increase (p < 0.05) in plasma vasopressin, which was also reversed by L-NAME. The effects of chloroquine on renal function and vasopressin secretion seem to be mediated by pathways involving nitric oxide. These data suggest that chloroquine may stimulate nitric-oxide synthase both centrally, stimulating vasopressin secretion, and within the kidney, where it modulates glomerular hemodynamics and tubular function. (+info)
Urethral pressure profile and hemodynamic effects of phenoxybenzamine and prazosin in non-sedated male beagle dogs.
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Prazosin is a readily available alpha-adrenergic antagonist that may be useful in the management of functional urethral obstruction in companion animals. This study used urethral pressure profilometry to evaluate the urethral effects of prazosin and phenoxybenzamine in healthy, non-sedated, male Beagle dogs. Heart rate, indirect systolic, diastolic and mean arterial blood pressures were measured, and saline perfusion urethral pressure profilometry was performed at 0, 10, 20, and 40 min following intravenous administration of prazosin (0.025 mg/kg), phenoxybenzamine (0.2 mg/kg), or placebo. Maximal urethral pressure, maximal urethral closure pressure, post peak nadir, and all blood pressure parameters decreased significantly at nearly all treatment intervals following administration of prazosin compared with placebo. Less consistently significant reductions were observed following phenoxybenzamine administration. Maximal decreases in urethral pressure parameters were observed 20 min following the injection of prazosin; maximal blood pressure decreases were evident by 10 min postinjection. In this non-sedated dog model, urethral pressure profilometry was a sensitive method of detecting urethral effects of alpha antagonists. Repeatable reductions in urethral pressure measurements were observed, with prazosin effecting more consistently significant changes than phenoxybenzamine. Significant decreases in systolic, diastolic, and mean arterial blood pressures were seen with prazosin, but not phenoxybenzamine or placebo. Further study of selective alpha-1 antagonists in dogs is needed to determine appropriate oral dosing protocols that will produce maximal urethral effects with minimal hemodynamic effects, and to demonstrate clinical efficacy in dogs with functional urethral obstruction. (+info)
Managing older patients with urinary retention in the Continence Clinic.
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OBJECTIVE: To evaluate the effectiveness of the Continence Clinic for managing retention of urine in older patients. DESIGN: Retrospective study. SETTING: Continence Clinic, Fung Yiu King Hospital, Hong Kong. SUBJECTS AND METHODS: Case notes of 58 patients seen at the Fung Yiu King Hospital Continence Clinic from October 1997 to September 2001 were reviewed. The patients had retention of urine with post-void residual volume of more than 200 mL, retention of urine requiring catheterization, or had catheters for unknown reasons. RESULTS: Urodynamic study performed for 22 (38%) patients showed that 12 had detrusor underactivity, six had detrusor hyperactivity with impaired contraction, and four had bladder outlet obstruction. Among the patients who were initially catheterized, the success rate for gradually stopping reliance on urinary catheterization was 84%. The success rate was higher among those who did not undergo urodynamic study than among those who had the study done (95% versus 67%; P=0.03). Reduction in post-void residual volume was observed at the last clinic visits (P<0.0001). Moreover, significant decreases in post-void residual volume were found both for patients who did and did not have urodynamic study. CONCLUSION: Most of the older patients with urinary retention with or without indwelling catheters were treated successfully in the Continence Clinic by appropriate medical therapy. Urodynamic study can be performed for selected patients when managing urinary retention. (+info)
Enalapril attenuates endothelin-1-induced hypertension via increased kinin survival.
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Recent studies have shown that angiotensin-converting enzyme (ACE) inhibitors attenuate endothelin-1 (ET-1)-induced hypertension, but the mechanisms for this effect have not been clarified. Initial experiments were conducted to contrast the effect of the ACE inhibitor enalapril, the combined ACE-neutral endopeptidase inhibitor omapatrilat, and the angiotensin II receptor antagonist candesartan on the hypertensive and renal response to ET-1 in anesthetized Sprague-Dawley rats. Acute intravenous infusion of ET-1 (10 pmol x kg(-1) x min(-1)) for 60 min significantly increased mean arterial pressure (MAP) from 125 +/- 8 to 145 +/- 8 mmHg (P < 0.05) and significantly decreased glomerular filtration rate (GFR) from 0.31 +/- 0.09 to 0.13 +/- 0.05 ml x min(-1) x 100 g kidney wt(-1). Pretreatment with enalapril (10 mg/kg iv) before ET-1 infusion inhibited the increase in MAP (121 +/- 4 vs. 126 +/- 4 mmHg) before and during ET-1 infusion, respectively (P < 0.05) without blocking the effect of ET-1 on GFR. In contrast, neither omapatrilat (30 mg/kg) nor candesartan (10 mg/kg) had any effect on ET-1-induced increases in MAP or decreases in GFR. To determine whether the effect of enalapril was due to the decrease in angiotensin II or increase in kinin formation, rats were given REF-000359 (1 mg/kg iv), a selective B(2) receptor antagonist, with or without enalapril before ET-1 infusion. REF-000359 completely blocked the effect of enalapril on ET-1 infusion (MAP was 117 +/- 5 vs. 135 +/- 5 mmHg before and during ET-1 infusion, respectively, P < 0.05). REF-000359 alone had no effect on the response to ET-1 infusion (MAP was 117 +/- 4 vs. 144 +/- 4 mmHg before and during ET-1 infusion, respectively, P < 0.05). REF-000359 with or without enalapril had no significant effect on the ability of ET-1 infusion to decrease GFR. These findings support the hypothesis that decreased catabolism of bradykinin and its subsequent vasodilator activity oppose the actions of ET-1 to increase MAP. (+info)
Urodynamic study of enhanced continent mechanism using tapered ileum as continent urinary reservoir.
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OBJECTIVE: To investigate the effect of extramural support from the pouch and abdominal wall to enhance the continent mechanism of tapered ileum. METHODS: A total of 24 patients underwent a procedure in which an ileal segment was tapered into an efferent tube, of which a part was placed between the back surface of the rectus muscle and the ileal pouch wall. The internal orifice of the tapered ileum was anastomosed to the ileal pouch and its external orifice was anastomosed to the umbilicus. A urodynamic study of the efferent tubes and pouch was done 1.5 to 3 months and 6 to 24 months postoperatively. RESULTS: One patient died of heart disease 55 days postoperatively, while 22 of the remaining 23 were completely continent day and night. At 1.5 to 3 months, the urodynamic study of the efferent tubes demonstrated that the maximum closure pressure with a full pouch was 46 - 124 cmH(2)O (91.26 +/- 15.71 cmH(2)O) and with an empty pouch was 34 - 84 cmH(2)O (67 +/- 10.60 cmH(2)O). The difference in mean maximum closure pressure in the full and empty pouches was statistically significant (t = -11.78 and P = 0.00001). At 6 to 24 months, a second urodynamic study was performed on 18 cases, demonstrating a reservoir capacity of 420 to 750 ml (481.67 +/- 78.83 ml). Reservoir pressure was 6 to 9 cmH(2)O (7.17 +/- 1.17 cmH(2)O) when the pouch was filled to 50 ml, and 16 to 35 cmH(2)O (24.12 +/- 5.61 cmH(2)O) when it was filled to maximum capacity. There was no contractive wave during the filling in any patient. Maximum closure pressure in the efferent tube was 80 to 194 cm H(2)O (98.89 +/- 26.34 cmH(2)O) when the pouch was filled with saline, and 64 to 128 cmH(2)O (74.78 +/- 14.54 cmH(2)O) when the pouch was empty. The difference in mean maximum closure pressure in the full and empty pouches was statistically significant (t = -7.58 and P = 0.00003). CONCLUSIONS: This study indicates that the continent mechanism of tapered ileum may be greatly enhanced by extramural support from the abdominal and pouch walls. (+info)