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Biomedical subjects

Robert M Levin

Publications and source records attributed to Robert M Levin.

At least 37 records · Page 2Linked to original sources
PubMed2005

Effect of age on rabbit bladder function and structure following partial outlet obstruction.

PURPOSE: We determined whether young and old rabbits respond differently to partial bladder outlet obstruction. MATERIALS AND METHODS: A total of 16 male New Zealand White rabbits were separated into 2 groups of 8 each. Group 1 consisted of young rabbits (age 7 weeks) and group 2 consisted of old rabbits (age 2 years). Four rabbits per group underwent partial outlet obstructions and 4 underwent sham operation. Four weeks following surgery individual bladder strips were used for contractile studies and the remaining tissue was examined histologically. RESULTS: Contractile responses to all forms of stimulation between the young and old sham operated groups were similar. Contractile responses to all forms of stimulation were significantly decreased to the same degree in the 2 obstructed groups. However, the rate of tension generation to field stimulation was decreased to a significantly greater degree in young vs old bladders. Although young and old bladders showed smooth muscle hypertrophy, older rabbits showed significantly greater thickening of the serosa than young rabbits. Young rabbits showed significant inflammation, hemorrhage and expansion of the lamina propria, whereas old rabbits showed none of these characteristics. CONCLUSIONS: Although there were only minor differences in the physiological response of young and old bladders to obstruction, young rabbits showed a significantly greater degree of histological damage. This may have been due to the thinner wall and greater sensitivity to distention.

Aging↗
PubMed2005

Effect of bladder ischaemia/reperfusion on superoxide dismutase activity and contraction.

OBJECTIVES: To correlate the effect of bilateral in-vivo bladder ischaemia/reperfusion on superoxide dismutase activity (SOD) and then to correlate this with contractile responses to various forms of stimulation. MATERIALS AND METHODS: Twenty mature male New Zealand White rabbits were divided into five equal groups: group 1 (controls); group 2, 2 h of in-vivo bilateral bladder ischaemia; and groups 3-5, 2 h of in-vivo ischaemia followed by 1, 7 or 14 days of reperfusion (recovery). At the end of the treatment period, bladder strips were incubated and placed in isolated baths for contractile studies. The contractile responses to field stimulation, carbachol (10 micromol/L), ATP and KCl were determined. The balance of the bladder body was separated into muscle and mucosa sections and analysed for SOD activity. RESULTS: There were few effects on contraction either directly after ischaemia or after 1 day of reperfusion. However, all contractile responses were significantly reduced at 7 and 14 days after ischaemia. SOD activity of the detrusor muscle was reduced significantly immediately after ischaemia and at 7 and 14 days of reperfusion. SOD activity of the mucosa was significantly greater than that of the muscle, and was significantly reduced by both ischaemia and all times of reperfusion. CONCLUSIONS: These studies show clearly that both ischaemia and reperfusion result in significantly lower activity of SOD, and in contractile dysfunctions, and that reperfusion results in greater decreases in both SOD activity and contractile responses than ischaemia alone.

Animals↗
PubMed2005

Protective effects of grape suspension on in vivo ischaemia/reperfusion of the rabbit bladder.

OBJECTIVE: To investigate the potential protective effect of a grape suspension in a rabbit model of in vivo bilateral ischaemia/reperfusion (I/R), which is a causal factor in obstructive bladder dysfunction. MATERIALS AND METHODS: Six groups of four New Zealand White rabbits were treated by twice-daily gavage with aqueous grape suspension (groups 1-3) or sugar-water vehicle (groups 4-6) for 3 weeks. Groups 1 and 4 then received bilateral ischaemia for 2 h, and groups 2 and 5 received bilateral ischaemia for 2 h and reperfusion (recovery) for 1 week. Groups 3 and 6 were controls (sham-operated). The effects on cystometry, in vitro contractile responses, and morphology were evaluated. RESULTS: Ischaemia resulted in significant reductions in the contractile responses to all forms of stimulation in vehicle-fed rabbits, whereas there were no reductions in grape-fed rabbits. Contractile responses were significantly reduced in both I/R groups, but significantly more in vehicle-fed than in grape-fed rabbits. Immunohistochemical studies showed less hypoxia in the bladders of grape-fed rabbits than in vehicle-fed rabbits for both ischaemia-only and I/R groups. CONCLUSIONS: Feeding rabbits with grape suspension provided significant protection against the hypoxic effects of bilateral ischaemia and I/R.

Animals↗
PubMed2005

Effect of nitric oxide synthase inhibition on changes induced by estradiol in bladders from ovariectomized rabbits.

PURPOSE: Our current study was designed to determine whether estradiol-induced increases in bladder blood flow could be inhibited by N(omega)-nitro-L-arginine methyl ester (L-NAME), and thus whether nitric oxide was involved in estrogen-linked female bladder blood flow alterations. MATERIALS AND METHODS: Sixteen female New Zealand White rabbits were separated into 4 groups of 4 rabbits each. (1) Sham group received sham operation and injections of vehicle (peanut oil). (2) Ovariectomy (OVX) group received ovariectomies and injections of vehicle. (3) Ovariectomy+estrogen (OVX+E) group received ovariectomy and injections of 17beta-estradiol (1 mg/kg) dissolved in peanut oil. (4) Ovariectomy+estradiol+L-NAME (OVX+E+L-NAME) group received ovariectomies and injections of 17beta-estradiol and L-NAME. All treatments were continued for 4 weeks. At 4 weeks after treatment, each rabbit was anesthetized and cystometries were performed. After cystometry, blood flow to the detrusor muscle and mucosa was determined by standard fluorescent microsphere infusion technique. Then four longitudinal detrusor strips and two rings of descending thoracic aorta were mounted in individual 15 ml baths containing oxygenated Tyrode's solution at 37 degrees C. Contractile responses to several agents were determined. Full-thickness sections of detrusor were fixed and embedded in paraffin for alpha-actin immunostaining. RESULTS: In the bladder: (1) Estradiol resulted in an increases in bladder weight and blood flow; L-NAME inhibited these increases. (2) OVX resulted in a decreased cystometric capacity; estradiol resulted in increased capacity which was attenuated by L-NAME treatment. (3) OVX resulted in significantly decreased contractile responses to all forms of stimulation; estradiol resulted in significantly increased contractile responses which were attenuated by L-NAME treatment. (4) OVX resulted in a significant decrease in the volume-fraction of smooth muscle in the detrusor; estradiol resulted in a significant increase which was attenuated by L-NAME. CONCLUSIONS: These findings strongly support the hypothesis that nitric oxide plays a major role in the alterations in blood flow mediated by changing circulating estrogen and that these changes mediate at least in part the cystometric and contractile changes induced by alterations in circulating estrogen.

Analysis of Variance↗
PubMed2004

Activation of mu opioid receptors in the ventrolateral periaqueductal gray inhibits reflex micturition in anesthetized rats.

This study tested the hypothesis that morphine and other opiates cause urinary retention by activating mu opioid receptors in the midbrain periaqueductal gray (PAG) region. Selective mu, delta and kappa receptor agonists were microinjected into the PAG of urethane-anesthetized rats and the amplitude and incidence of bladder contractions were recorded during continuous saline infusion. Arterial pressure was monitored through a femoral artery catheter. Microinjection of the mu receptor agonist DAMGO into the ventrolateral PAG (vlPAG) suppressed volume-evoked bladder contractions completely. Bladder contractions ceased within 5 min of DAMGO injection and remained essentially undetectable for the rest of the 20 min recording period. Microinjection of the delta receptor agonist DPDPE into the vlPAG did not significantly affect either the amplitude of bladder contractions or the time interval separating contractions. The kappa receptor agonist U-69593 caused no discernible change in amplitude but increased the interval between bladder contractions significantly. Microinjection of DAMGO, DPDPE or U-69593 into the lateral or dorsolateral PAG columns was ineffective. DAMGO injection into the vlPAG increased arterial pressure whereas DPDPE and U-69593 produced a small but significant depressor response. These data support the hypothesis that mu and kappa receptors in the vlPAG participate in the micturition reflex.

Administration, Intravesical↗
PubMed2004

Outbreak of necrotizing fasciitis due to Clostridium sordellii among black-tar heroin users.

In California, black tar heroin (BTH) use among injection drug users (IDUs) has resulted in an increased number of cases of wound botulism due to Clostridium botulinum, tetanus due to Clostridium tetani, and necrotizing soft-tissue infections due to a variety of clostridia. From December 1999 to April 2000, nine IDUs in Ventura County, California, developed necrotizing fasciitis; 4 died. Cultures of wound specimens from 6 case patients yielded Clostridium sordellii. Some of the patients appeared to have the toxic shock syndrome previously reported to be characteristic of toxin-mediated C. sordellii infection, which is characterized by hypotension, marked leukocytosis, and hemoconcentration. The suspected source of this outbreak was contaminated BTH that was injected subcutaneously or intramuscularly ("skin popped"). This outbreak of C. sordellii infection serves as another example of how BTH can potentially serve as a vehicle for transmitting severe and often deadly clostridial infections, and reinforces the need to educate IDUs and clinicians about the risks associated with skin popping of BTH.

Adult↗
PubMed2004

Oral Kohki Tea and its protective effect against in vitro ischemic damage to the bladder.

AIMS: Results of several studies indicate that ischemia/reperfusion (I/R) is an etiological factor in the contractile dysfunctions induced by partial bladder outlet obstruction in animal models. In support of this hypothesis, pretreatment of rabbits with Kohki Tea (Engelhardtia chrysolepis), a Japanese herbal drink very high in antioxidant activity, significantly reduced the contractile dysfunctions induced by partial outlet obstruction. The current study was designed to determine if pretreating rabbits with Kohki Tea could protect the bladder against the contractile damage induced by in vitro ischemia followed by re-oxygenation. METHODS: Forty-eight New Zealand White rabbits were separated into two groups of 24; Group 1 was pretreated by oral gavage for 3 weeks with Kohki Tea and Group 2 received vehicle (water). Each rabbit was anesthetized with pentobarbital. The urinary bladder was rapidly removed and eight longitudinal muscle strips were cut from the bladder body. Each strip was mounted in a separate 15-ml bath containing Tyrode's solution with glucose (1 mg/ml) and maintained at 37 degrees C. All strips were equilibrated for 30 min with a gas mixture of 95% O2 and 5% CO2. At the end of this period of time, all strips were stimulated with field stimulation (FS) carbachol and KCl. After the last wash, the aeration was changed to hypoxic mixture (nitrogen-CO2) without glucose. At the end of 2 hr, the aeration was changed back to the normal 95% O2 and 5% CO2, and glucose was added to the buffer. After 1 hr of re-oxygenation, a second set of stimulations was performed. In order to represent hyperreflexia, the strips were stimulated at 32-Hz FS at 5-min intervals during the hypoxic period in half of the in vitro experiments. RESULTS: The results showed that Kohki Tea pretreatment protected the bladder's response to FS from the detrimental effects of repetitive stimulation and the detrimental effects of both in vitro ischemia and repetitive stimulation on the contractile responses to carbachol and KCl. CONCLUSIONS: These data are consistent with the concept that Kohki Tea acts by protecting the bladder from cellular damage caused by hypoxia and the generation of free radicals.

Administration, Oral↗
PubMed2004

Protection of urinary bladder function by grape suspension.

Urinary bladder dysfunction secondary to BPH is a major affliction of aging men. A rabbit model of partial outlet obstruction was used to evaluate the ability of a standardized grape suspension to protect the bladder against obstructive bladder dysfunction.Twenty-four New Zealand White rabbits were separated into four groups of six rabbits each. Groups 1 and 3 were pretreated by oral gavage for 3 weeks with a standardized grape suspension suspended in water; groups 2 and 4 were treated with vehicle. Groups 1 and 3 received sham operations after 3 weeks of treatment; groups 2 and 4 received partial outlet obstruction by surgically placing a silk ligature loosely around the urethra. At 3 weeks following surgery, in vivo and in vitro bladder functions were evaluated. Based on both in vivo and in vitro studies, the grape suspension significantly reduced the severity of obstructed bladder dysfunction. This is consistent with the hypothesis that ischemia is a major etiological factor in obstructive dysfunction, and treatment with antioxidants and membrane stabilization compounds such as those in the grape suspension can be effective in the treatment of obstructive bladder pathology.

Adrenergic alpha-Antagonists↗
PubMed2004

Effect of timing of diuresis on response of rat bladder to outlet obstruction.

OBJECTIVES: To determine whether results similar to a previous study, in which sucrose-induced diuresis started before creating partial outlet obstruction resulted in protection of bladder contractile function in obstructed animals, would be obtained if diuresis were begun after creation of partial outlet obstruction. METHODS: Thirty-six rats were separated into six groups of 6 rats each: group 1, control; group 2, diuresis; group 3, obstructed; group 4, obstructed immediately after diuresis; group 5, obstructed with diuresis beginning 10 days after obstruction; and group 6, obstructed before diuresis. Diuresis was induced by feeding 5% sucrose instead of water. After 3 weeks of obstruction, all bladders were excised, cut into longitudinal strips, and mounted in isolated muscle baths for physiologic study. RESULTS: Sucrose-induced diuresis resulted in a statistically significant increase in bladder mass and a mild increase in smooth muscle contractility compared with the control water-fed group. Obstruction resulted in a fourfold increase in bladder weight and substantial decreases in the responses to all forms of stimulation. The bladder weights of the obstruction plus diuresed groups were all similar to the diuresis-alone group and significantly lower than those of the obstructed group. All diuresed groups showed protection of the contractile responses compared with the obstruction-alone group. Unexpectedly, the group that began diuresis 1 day after obstruction showed the strongest protection. CONCLUSIONS: Diuresis significantly reduced the increase in bladder mass induced by obstruction and also reduced the level of contractile dysfunction. Diuresis begun 1 day after obstruction resulted in the greatest level of protection.

Animals↗
PubMed2004

Effects of castration on female rabbit bladder physiology and morphology.

OBJECTIVES: To determine the effect of ovariectomy on bladder blood flow and oxygen tension. Women are subject to bladder dysfunctions that occur less frequently in men. These include interstitial cystitis (syndrome of urgency, frequency, and pain on distension), incontinence, and bladder infections. It is believed that alterations in female sex hormones play a major role in mediating these abnormalities. We believe that alterations in estrogen can have marked effects on the blood flow to the bladder. METHODS: We divided 20 female rabbits into two equal groups: ovariectomized and sham operated. Six weeks later, the bladder of each rabbit was evaluated for bladder capacity, compliance, permeability, blood flow, tissue hypoxia, morphology, and smooth muscle contraction. RESULTS: Ovariectomy resulted in decreased bladder compliance; decreased blood flow to the bladder mucosa and uterus, a smaller decrease in blood flow to the bladder smooth muscle, and mucosal hypoxia; and statistically significant thinning of the bladder mucosa and increased mucosal permeability. CONCLUSIONS: Ovariectomy resulted in decreased blood flow and hypoxia to the bladder mucosa and a mildly decreased blood flow to the smooth muscle. The decreased blood flow and hypoxia may be related to the age-related uropathologic findings in postmenopausal women.

Age Factors↗
PubMed2004

Inhibition of hyperreflexia by vaginally administered oxybutynin: a novel rabbit model.

PURPOSE: The rabbit has proved to be an excellent model in which to study lower urinary tract function and pathological mechanisms involved in specific forms of lower urinary tract dysfunctions, including those involved with partial outlet obstruction (benign prostatic hyperplasia), erectile dysfunction, bladder instability and ischemic bladder disease. The current study describes a model of bladder instability induced in female rabbits and its use in developing a novel form of vaginal treatment for this instability. MATERIALS AND METHODS: A total of 18 female New Zealand White rabbits were used for this experiment. Each rabbit was anesthetized and the carotid artery was cannulated for blood pressure monitoring. The bladder dome was catheterized for monitoring bladder pressure and for cystometry. A ligature was placed around the urethra just distal to the bladder neck to prevent leakage through the urethra and generate unstable bladder contractions. After initial cystometry the bladder was emptied and then filled to 30 ml. Acetylcholine (Ach) was administered into the vesical artery at 15-minute intervals for 2 hours. Hyperreflexia usually developed within 30 minutes. Vaginal oxybutynin (low and high dose) was applied and the effect on cystometry, the response to Ach, and the amplitude and frequency of hyperreflexia was determined. RESULTS: Each dose of oxybutynin increased bladder capacity and improved compliance. The high oxybutynin dose completely inhibited the response to Ach and significantly decreased micturition pressure. The high dose decreased uninhibited bladder contraction peak pressure in a time dependent manner to a greater extent than it decreased uninhibited contraction frequency. The low dose of oxybutynin had no effect on micturition pressure, significantly inhibited the response to Ach and hyperreflexia amplitude to approximately 40% of control values, and had little effect on hyperreflexia frequency. CONCLUSIONS: Vaginally delivered oxybutynin was effective in improving bladder compliance, inhibiting intra-arterial Ach stimulated bladder contractions and significantly decreasing the amplitude of hyperreflexia. Vaginal oxybutynin had a more potent effect on the evoked response to Ach and on hyperreflexia than it did on micturition pressure.

Administration, Intravaginal↗
PubMed2004

The molecular genetic basis of mitochondrial malfunction in bladder tissue following outlet obstruction.

PURPOSE: Bladder dysfunction following partial outlet obstruction is a frequent consequence of benign prostatic hyperplasia and an increasingly common problem given the aging of the general population. Recent studies from this and other groups have begun to elucidate the molecular bases for the well described physiological malfunctions that characterize this clinical entity. We summarized and synthesized that information. MATERIALS AND METHODS: Using modern methods of molecular genetics, including real-time polymerase chain reaction, real-time reverse transcriptase-polymerase chain reaction and others, as well as traditional experimental techniques such as electron microscopy we and others examined the transcriptional profile, morphology, etc of bladder smooth muscle mitochondria in experimental models of outlet obstruction. RESULTS: Data from many studies have demonstrated that aberrant gene expression in the mitochondrial and mitochondria related nuclear genetic systems underlies the loss of compliance and other attributes of bladder dysfunction following outlet obstruction. Such aberrant transcriptional characteristics engender loss of function in the electron transport and oxidative phosphorylation systems. Morphological studies of mitochondria in the animal model systems support this conclusion. CONCLUSIONS: In large part the loss of function in bladder smooth muscle following outlet obstruction results from the attenuation of mitochondrial energy production. In this article we reviewed and synthesized all available experimental observations relevant to this problem and we suggest future lines of inquiry that should prove fruitful in developing new strategies to treat the condition.

Animals↗
PubMed2003

Hypoxia preconditioning attenuates bladder overdistension-induced oxidative injury by up-regulation of Bcl-2 in the rat.

We explored whether hypoxic preconditioning minimizes oxidative injury induced by overdistension/emptying in the rat bladder. For hypoxic preconditioning, female Wistar rats were placed in a hypobaric chamber (380 Torr) 15 h day(-1) for 28 days. Overdistension was induced by infusion of two times the threshold volume of saline into the bladder and was maintained for 1 or 2 h, followed by drainage/emptying. During overdistension (ischaemia) and emptying (reperfusion) periods, a bursting increase of reactive oxygen species (ROS) from the bladder was originated from the large numbers of infiltrating leucocytes and scattered resident cells, including urothelial, submucosal, and smooth muscle cells. ROS impaired the voiding function by a reduction of bladder afferent and efferent nerve activity and bethanecol- or ATP-induced detrusor contraction. ROS enhanced pro-apoptotic mechanisms, including increases in the Bax/Bcl-2 ratio, CPP32 expression, and poly(ADP-ribose) polymerase (PARP) fragments with subsequent apoptotic cell formation in the insulted bladders. Hypoxia preconditioning up-regulated Bcl-2 expression in the bladder and significantly reduced the levels of ROS and apoptosis detected in the overdistension/emptying bladders and preserved partial voiding function. Bcl-2 up-regulation by hypoxia preconditioning contributes protection against overdistension/emptying-induced oxidative stress and injury in the bladder.

Animals↗
PubMed2003

Effect of the Bowman-Birk inhibitor (a soy protein) on in vitro bladder neck/urethral and penile corporal smooth muscle activity.

AIMS: The Bowman-Birk inhibitor (BBI), is a serine protease inhibitor derived from soy beans, which is presently being evaluated in clinical trials for its ability to serve as a cancer preventive or anti-inflammatory agent. The form of BBI currently in clinical trials is known as Bowman-Birk inhibitor concentrate (BBIC). There have been anecdotal reports from patients of improved voiding and sexual functions in the ongoing BBIC trials. The objective of this study was to quantify the effect of BBI and BBIC on urethral and corporal smooth muscle activity. METHODS: In vitro muscle strip studies of New Zealand White rabbit urethra/bladder neck and penile corpora in the presence or absence of BBI or BBIC incubation (5 mg/mL) were performed. RESULTS: In dose-response curves to alpha stimulation, BBI mediated a shift to the right (decreased receptor sensitivity in bladder/urethra as well as corpora with no change in the maximal response). Bladder base/ urethra contraction by field stimulation was significantly inhibited by BBI at higher frequencies (1-32 Hz) (12.2 + 0.8 g vs. 6.3 + 0.75 g, P < 0.05). BBI inhibited field stimulated relaxation of corporal muscle at lower frequencies. Muscarinic contraction of the bladder neck/urethra in alpha prestimulated tissue was significantly inhibited by BBI (5.3 + 0.2 g vs. 2.7 + 0.1 g, P < 0.05). BBI has an inhibitory effect on alpha adrenergic dose-response curves in bladder neck/urethral and corpora smooth muscle. BBI also significantly inhibited neurohumoral cholinergic release and in vitro muscarinic contraction of the urethra. The effects on corpora relaxation were less pronounced. CONCLUSIONS: The data suggest that the phytochemical BBI may promote physiologic effects of urethral relaxation and improved voiding by unique mechanisms and deserves further study as a pharmacologic agent for lower urinary tract symptoms.

Adrenergic alpha-Agonists↗
PubMed2003

Focal hypoxia of the obstructed rabbit bladder wall correlates with intermediate decompensation.

AIMS: We showed that partial obstruction of the rabbit bladder outlet caused decreases in detrusor blood flow that were directly proportional to the level of decompensation present. Bladder decompensation is characterized by decreases in detrusor contractility, mitochondrial function, and sarco/endoplasmic reticulum calcium ATPase (SERCA) activity in obstructed rabbits. The current study was designed to create bladder decompensation and to relate its characteristic dysfunctions to the presence or absence of hypoxia in the obstructed rabbit bladder wall. Tissue hypoxia was visualized immunohistochemically after administration of a hypoxia probe in vivo. METHODS: Twelve New Zealand White rabbits were separated into two groups. The rabbits in group 1 received sham operations; the rabbits in group 2 received partial outlet obstructions by standard methods. Four weeks after surgery, each rabbit received an intraperitoneal injection of aqueous Hypoxyprobe-1, which forms protein adducts in cells having O(2) concentrations less than 14 microM. Two hours after injection, the rabbit was anesthetized and the bladder exposed through a midline incision. One full-thickness bladder strip was cut and immediately placed in fixative for immunohistochemical recognition and visualization of Hypoxyprobe-1-protein adducts. The remaining bladder was then excised, and three additional strips were cut for contractility studies. The remainder of the bladder was frozen for biochemical and slot-blot analyses. RESULTS: Bladder weight was increased fourfold after obstruction, and significant contractile and biochemical dysfunctions were observed that indicated an intermediate level of decompensation. Immunohistochemical visualization revealed focal areas of moderate to severe hypoxia in the detrusor smooth muscle (SM) and subserosal regions of these bladders. No hypoxia was observed in the obstructed bladder mucosa, consistent with the absence of biochemical dysfunction in this compartment, or in unobstructed bladders. Slot-blot analyses confirmed the presence of significant Hypoxyprobe-1-protein adducts in the detrusor of the obstructed bladder, whereas none were present in the control bladder detrusors. CONCLUSIONS: Partial outlet obstruction of rabbit bladders resulted in focal areas of moderate to severe hypoxia in the detrusor SM and subserosal regions concomitant with increased bladder mass, decreased contractile function, and selective metabolic dysfunctions of the SM consistent with an intermediate stage of decompensation. The metabolic characteristics of the normoxic mucosa were normal a were those of unobstructed bladders.

Adenosine Triphosphate↗
PubMed2003

Effectiveness of vaginally administered oxybutynin on rabbit bladder function.

OBJECTIVES: To demonstrate the effectiveness of vaginally delivered oxybutynin on bladder function. Oxybutynin has been used for treatment of urge urinary incontinence for more than 20 years. METHODS: Thirty female New Zealand White rabbits were used for this experiment. Each rabbit was anesthetized, and the carotid artery was cannulated for blood pressure monitoring. The bladder dome was catheterized for both monitoring of bladder pressure and cystometry. After initial cystometry, acetylcholine (ACh) was injected into the vesical artery at 15-minute intervals for 4 hours. Cystometry was performed at the 2-hour mark and at the end of each experiment (4 hours). After the third ACh administration, vaginal or oral oxybutynin was given and the effect on the response to ACh, blood pressure, and cystometry was observed. RESULTS: The high dose of oxybutynin completely inhibited the response to ACh and significantly inhibited the micturition reflex. A 45% inhibition of micturition pressure occurred at the intermediate dose. Little effect on compliance after the low dose and a significant increase in compliance after the mid-dose occurred. Both the low and intermediate doses of oxybutynin reduced the response to ACh to approximately 50% of control. No blood pressure effects of vaginal oxybutynin were noted for any concentration. Oral oxybutynin showed very similar effects to that of the intermediate vaginal dose. CONCLUSIONS: Vaginally delivered oxybutynin was effective in decreasing bladder compliance and inhibiting intra-arterial ACh-stimulated bladder contractions with little or no effect on the vascular effect of ACh.

Acetylcholine↗