Effect of endothelin on bladder contraction: potential role in bladder hyperactivity.
In the present study, we demonstrate that the intravenous infusion of endothelin-1 (3 and 10 ng/kg/min) causes a decrease in the mean micturition volume of rats in addition to an increase in mean arterial pressure. These effects are blocked by both the ET(A)/ET(B)-non-selective and the ET(A)-selective endothelin antagonists SB 217242 and SB 247083 respectively (both 30 mg/kg). However, it was also observed that the ET(B)-selective agonist sarafotoxin 6c (3 and 10 ng/kg/min) had similar effects on both mean arterial pressure and micturition volume. Initial experiments indicated that spontaneously hypertensive rats have a much lower mean micturition volume than normal rats. Binding studies comparing the total number and ratio of ET(A)/ET(B) receptors in spontaneously hypertensive, Wister-Kyoto and Sprague-Dawley rats revealed no significant differences in receptor expression. However, the magnitude of the response to endothelin-1 was greater in spontaneously hypertensive versus normal rats.
Westfall
Timothy D
TD
Department of Renal and Urology Research, GlaxoSmithKline, King of Prussia, PA 19406-0939, USA. timothy_d_westfall@gsk.com
McCafferty
Gerald P
GP
Pullen
Mark
M
Ventre
Jessica
J
Eybye
Marianne
M
Jugus
Malcolm J
MJ
Brooks
Stuart A
SA
Hieble
J Paul
JP
Brooks
David P
DP
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D002264:Carboxylic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology; D007189:Indans / Q000494:pharmacology; D007262:Infusions, Intravenous; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000502:physiology*; D014554:Urination / Q000187:drug effects; D014555:Urination Disorders / Q000139:chemically induced / Q000503:physiopathology
D001572:Benzofurans; D002264:Carboxylic Acids; D016232:Endothelins; D007189:Indans; D011422:Propionates; C113045:SB 247083; C098288:enrasentan