PURPOSE: To investigate the role of muscarinic receptors in bladder sensory mechanism. MATERIALS AND METHODS: Normal adult volunteers collected voided urine after taking five days of trospium(20 mg bid), tolterodine LA(4 mg qd) and oxybutynin XL(10 mg qd). The effect of intravesical administration of human urine on carbachol-induced bladder overactivity was studied in female Sprague-Dawley rats. Cystometric parameters during continuous infusion for over one hour each of saline, human urine, then mixture of carbachol and human urine were compared(n=6 in each group). Then 0.1 and 0.5microgram/ml of oxybutynin, trospium, tolerodine, and dimethindene were studied with the same methods. RESULTS: Human urine with or without intake of antimuscarinic agents had no effect on normal bladder function. Bladder capacity and intercontraction intervals were significantly decreased after an addition of carbachol to human urine containing vehicle, tolterodine or oxybutynin. Human urine after ingestion of trospium, however, prevented the carbachol-induced reduction in bladder capacity and intercontraction intervals. Maximum voiding pressure and pressure threshold were not changed in any case. 0.1 and 0.5microgram/ml of oxybutynin, trospium, tolerodine, and dimethindene prevented the decrease of intercontraction interval with intravesical carbachol(65+/-0.1% compared with baseline). CONCLUSION: The excreted urine after oral ingestion of 20 mg bid of trospium has a significant inhibitory effect in a rat model of detrusor overactivity. Intravesical instillation of antimuscarinic agents at clinically meaningful concentrations also suppressed carbachol-induced bladder overactivity. Antimuscarinic agents may be effective in treating bladder overactivity, not only by suppression of muscarinic receptor-mediated detrusor muscle contraction, but also by blocking muscarinic receptors in bladder-afferent pathways.
Administration, Intravesical ; Adult ; Carbachol ; Dimethindene ; Eating ; Female ; Humans ; Models, Animal ; Muscarinic Antagonists* ; Muscle Contraction ; Rats, Sprague-Dawley ; Receptors, Muscarinic* ; Urinary Bladder* ; Urinary Bladder, Overactive ; Volunteers ; Tolterodine Tartrate

We performed a randomized, prospective study to evaluate the effect of intraoperative, intracameral carbachol or acetylcholine on early postoperative intraocular pressure(IOP) after extracapsular cataract extraction(ECCE) and posterior chamber lens(PCL) implantation. Fifty-six eyes of 56 patients scheduled for routine ECCE and PCL implantation were randomly assigned into three groups: (1)carbachol infusion (19 eyes) (2) acetylcholine infusion (15 eyes) (3)balanced salt solution (BSS) infusion (control, 22 eyes). We compared the preoperative IOP, early postoperative IOP, postoperative 24 hours IOP and postoperative 1 week IOP. In the measurement of early postoperative IOP, IOP was measured at least twice at 3, 6 or 9 hours postoperatively. There was no significant difference in IOP between the three groups preoperatively, at postoperative 3 hours, and 1 week. At postoperative 6 hours, both the carbachol infusion group and acetylcholine infusion group were significantly different from the BSS infusion group. At postoperative 9 and 24 hours, only carbachol infusion group had a significant difference from BSS infusion group in suppression of postoperative IOP increase. Our results suggest that intraoperative, intracameral administration of carbachol or acetylcholine prevents early postoperative IOP increase, and that carbachol has a more lasting effect.
Acetylcholine/administration & dosage/*pharmacology ; Adult ; Aged ; Anterior Chamber/drug effects ; Carbachol/administration & dosage/*pharmacology ; Cataract Extraction/*adverse effects ; Female ; Humans ; Intraocular Pressure/*drug effects ; Lenses, Intraocular ; Male ; Middle Aged ; Ocular Hypertension/etiology/*prevention & control ; Postoperative Complications ; Prospective Studies

OBJECTIVETo investigate the effect of carbachol(CAR) on oxygen dynamic parameters and hyperlactacidemia during oral fluid resuscitation of burn shock.

METHODSTwelve male Beagle dogs were surgically prepared for cannulation of carotid and jugular vein, and enterostomy, 24 hours later they were subjected to a 50% (total body surface area, TBSA) full-thickness flame injury under a 10-15 minute anesthesia by IV injection of propofol. The dogs were randomized to gastric fluid infusion group (GI group)and gastric fluid infusion plus CAR group (GI + CAR). Either a glucose-electrolyte solution(GES) or GES containing CAR (20 microg/kg) were intragastricly given to animals in GI group or GI+ CAR groups. The delivery rate and volume of GES was in accordance with that of Parkland formula. Mean arterial pressure (MAP), intestinal mucosal blood flow (IMBF) and blood lactic acid were determined, and blood gas analysis evaluated for oxygen delivery (DO2), oxygen consumption (VO2) and oxygen uptake (O2ext) at 0, 2, 4, 8, 24, 48 and 72 hours after injury.

RESULTSThe levels of MAP and IMBF markedly reduced, and LAC obviously increased in both groups after burn. MAP returned to 0 h level at 72 h post burn, while IMBF, and LAC were still higher or lower than 0 h levels. The level of MAP of GI + CAR group was significantly higher than that of GI group at 2 h, and those showed no significant differences between two groups after then. Carbochol administration led to a markedly higher levels of IMBF, and significant lower levels of LAC from 8 h after burn compared with those of GI group (P < 0.05 or P < 0.01). The levels of DO2 VO2 and Oext were reduced markedly after burn in both groups. At 72 h after burn, DOQ returned to 0 h level; while VO2 and Oext though still much lower than 0 h levels. The level of DO2. VO2 and Oext of GI + CAR group were significantly higher than those of GI group from 8 h after burn (P < 0.05 or P < 0.01). Three of six animals died in GI+ CAR group, which was lower than two of six in GI group.

CONCLUSIONThe results indicates that carbachol promotes intragastric fluid resuscitative effect of burn shock by increasing oxygen delivery and decreasing hyperlactacidemia.

Animals ; Burns ; complications ; physiopathology ; therapy ; Carbachol ; pharmacology ; Dogs ; Electrolytes ; administration & dosage ; Fluid Therapy ; methods ; Glucose ; administration & dosage ; Intestinal Absorption ; drug effects ; Male ; Oxygen ; metabolism ; Resuscitation ; methods ; Shock ; etiology ; physiopathology ; therapy

OBJECTIVETo investigate the effect of AT₁ receptor on the changes of tyrosine hydroxylase-immunoreactivity (TH-IR) in rostral ventrolateral medulla (RVLM) induced by brain cholinergic stimuli in rats.

METHODSMale SD rats were randomly divided into 4 groups: NS + CBC group, Los + CBC group, Los + NS group and NS + NS group. AT₁ was blocked by pretreatment of 20 μg losartan in Los + CBC and Los + NS groups; intracerebroventricular injection of 0.5 μg carbachol was used for cholinergic stimuli in NS + CBC and Los + CBC groups; normal saline (NS) was used for control. The output amount of natrium in kidney, glomerular filtration rate (GFR) and renal plasma flow (PRF) were observed. The changes of TH-IR in the RVLM were observed by immunohistochemistry.

RESULTIn NS + CBC group carbachol induced potent natriuresis, after pretreatment of losartan the natriuretic effect was partially inhibited in Los + CBC group. Both the number and optical density of TH-IR positive neurons in NS + CBC group were markedly increased than those in NS + NS group (P < 0.05); while those in Los + CBC group were significantly lower than those in NS+CBC group (P < 0.05). Intracerebroventricular injection of carbachol and losartan had no effect on GFR and RPF(P > 0.05).

CONCLUSIONThe results suggest that cholinergic stimuli can induce potent natriuresis and increase the activity of adrenergic neurons in the RVLM; the above effects can be down regulated by blockade of brain AT₁ receptor.

Animals ; Carbachol ; administration & dosage ; pharmacology ; Drug Antagonism ; Glomerular Filtration Rate ; drug effects ; Losartan ; pharmacology ; Male ; Medulla Oblongata ; drug effects ; metabolism ; Natriuresis ; drug effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptor, Angiotensin, Type 1 ; physiology ; Tyrosine 3-Monooxygenase ; metabolism