Role of supraspinal tachykinins for micturition in conscious rats with and without bladder outlet obstruction.
In order to clarify the role of supraspinal tachykinins in volume-induced micturition and in bladder hyperactivity secondary to bladder outlet obstruction, conscious, normal, female Sprague-Dawley rats were investigated cystometrically before and after intracerebroventricular administration of RP 67,580, a selective antagonist of neurokinin (NK)-1 receptors and/or SR 48,968, a selective antagonist of NK-2 receptors. In normal rats, RP 67,580 or SR 48,968, at a dose of 2 nmol, caused no marked changes in cystometric parameters. Higher doses (up to 20 nmol) caused dose-dependent decreases in micturition pressure and increased bladder capacity, micturition volume and residual urine. A combination of the two drugs, each at a dose of 2 nmol, significantly decreased micturition pressure and increased bladder capacity. In rats with bladder outlet obstruction, the antagonists suppressed micturition dose-dependently, producing urinary retention in two out of eight rats already at a dose of 2 nmol. At a dose of 20 nmol, dribbling incontinence, due to urinary retention, was seen in five out of ten rats. A combination of the two drugs (2 nmol of each drug) caused urinary retention in three out of nine animals and significantly increased bladder capacity, micturition volume and residual volume. The results suggest that outflow obstruction in rats increases the effects of tachykinins in supraspinal structures involved in micturition, and that antagonism of supraspinal NK-receptors may depress the micturition reflex. Whether or not this implies that supraspinal NK-receptors can be targets for drugs aimed for inhibiting bladder hyperactivity in humans should be explored.
Gu
B J
BJ
Department of Urology, Shinshu University School of Medicine, Asahi, Matsumoto, Japan.
Ishizuka
O
O
Igawa
Y
Y
Nishizawa
O
O
Andersson
K E
KE
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002404:Catheterization; D005260:Female; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D008751:Methylene Blue / Q000378:metabolism; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D015320:Tachykinins / Q000502:physiology*; D014018:Tissue Distribution; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*; D001748:Urinary Bladder Neck Obstruction; D014549:Urinary Incontinence / Q000378:metabolism*; D014554:Urination / Q000187:drug effects / Q000502:physiology*
D000700:Analgesics; D001549:Benzamides; D007211:Indoles; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018041:Receptors, Neurokinin-2; D015320:Tachykinins; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; C073839:SR 48968; D008751:Methylene Blue