Evaluation of pressor and visceromotor reflex responses to bladder distension in urethane anesthetized rats.
OBJECTIVE
We tested cardiovascular and visceromotor reflex (VMR) responses to urinary bladder distension (UBD) in urethane anesthetized rats to see if it can replicate the response pattern and the inhibition of bladder nociceptive transmission by analgesics seen in isoflurane anesthetized animals.


METHODS
Female Sprague-Dawley rats under 3% isoflurane anesthesia were acutely instrumented with jugular venous, carotid arterial, and bladder cannulas for drug administration, blood pressure (BP) measurement, and bladder distension, respectively. Needle electrodes were placed directly into the abdominal musculature to measure myoelectrical activity subsequent to phasic UBD (30 sec in 3 min intervals). A cardiovascular response (pressor) and a VMR response (a contraction of abdominal and hind limb musculature) to UBD were evaluated in urethane (1.2 g/kg, i.v.) or isoflurane (1%) anesthetized rats.


RESULTS
Pressor and VMR responses to noxious UBD (60 mmHg) were generated under both anesthesics. The thresholds of stimulus response functions for both pressor and VMR responses were not affected by either anesthesics. However, the magnitude of the maximal pressor response was significantly reduced in urethane anesthesia. The analgesics, morphine, and mexiletine, significantly inhibited the VMR response to noxious UBD under both anesthetics, but the intensities of the inhibition from both analgesics under urethane anesthesia were much lower than under isoflurane anesthesia (ID50: 2.07 mg/kg vs. 0.88 mg/kg for morphine, >10 mg/kg vs. 0.47 mg/kg for mexiletine).


CONCLUSIONS
The rat urinary bladder distension model in urethane anesthetized rats demonstrates a blunted maximal pressor response and a reduced inhibition of visceral nociceptive transmission by analgesics. Neurourol. Urodynam. 28:442-446, 2009. (c) 2008 Wiley-Liss, Inc.
Blatt
Lauren K
LK
GlaxoSmithKline Pharmaceuticals, Department of Urology, King of Prussia, Pennsylvania, USA.
Lashinger
Erin S R
ES
Laping
Nicholas J
NJ
Su
Xin
X
D000009:Abdominal Muscles / Q000294:innervation*; D000700:Analgesics / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000294:innervation*; D004305:Dose-Response Relationship, Drug; D004576:Electromyography; D005260:Female; D007530:Isoflurane / Q000494:pharmacology; D040542:Mechanotransduction, Cellular / Q000187:drug effects*; D008801:Mexiletine / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects*; D014520:Urethane / Q000494:pharmacology*; D001743:Urinary Bladder / Q000294:innervation*
D000700:Analgesics; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D008801:Mexiletine; D014520:Urethane; D009020:Morphine; D007530:Isoflurane