Analysis of the afferent limb of the vesicovascular reflex using neurotoxins, resiniferatoxin and capsaicin.
The afferent limb of the vesicovascular reflex (VV-R) evoked by distension or contraction of the urinary bladder (UB) was studied in urethane-anesthetized female rats by examining the changes in VV-R after administration of C-fiber afferent neurotoxins [capsaicin and resiniferatoxin (RTX)]. Systemic arterial blood pressure increased parallel (5.1 to 53.7 mmHg) with graded increases in UB pressure (20 to 80 cm H(2)O) or during UB contractions. The arterial pressor response to UB distension was significantly reduced (60-85%) by acute or chronic (4 days earlier) intravesical administration of RTX (100-1,000 nM) or by capsaicin (125 mg/kg sc) pretreatment (4 days earlier). Chronic neurotoxin treatments also increased the volume threshold (>100%) for eliciting micturition in anesthetized rats but did not change voiding pressure. Acute RTX treatment (10-50 nM) did not alter the arterial pressor response during reflex UB contractions, whereas higher concentrations of RTX (100-1,000 nM) blocked reflex bladder contractions. It is concluded that VV-R is triggered primarily by distension- and contraction-sensitive C-fiber afferents located, respectively, near the luminal surface and deeper in the muscle layers of the bladder.
Chuang
Y C
YC
Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
Fraser
M O
MO
Yu
Y
Y
Beckel
J M
JM
Seki
S
S
Nakanishi
Y
Y
Yokoyama
H
H
Chancellor
M B
MB
Yoshimura
N
N
de Groat
W C
WC
D000283:Administration, Intravesical; D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002211:Capsaicin / Q000008:administration & dosage; D004106:Dilatation; D004224:Diterpenes / Q000008:administration & dosage; D005260:Female; D007279:Injections, Subcutaneous; D009119:Muscle Contraction / Q000502:physiology; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009498:Neurotoxins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D001743:Urinary Bladder / Q000294:innervation / Q000502:physiology*; D014554:Urination / Q000187:drug effects
D004224:Diterpenes; D009498:Neurotoxins; C024353:resiniferatoxin; D002211:Capsaicin