Effect of KW-7158, a putative afferent nerve inhibitor, on bladder and vesico-vascular reflexes in rats.
The effects of KW-7158, a putative afferent nerve inhibitor, on reflex bladder activity and vesico-vascular reflexes were evaluated in urethane anesthetized SD rats with normal and xylene-irritated bladders. The bladder was filled with saline until the appearance of large amplitude spontaneous bladder contractions (LA-BC). Vesico-vascular reflexes were measured as increases in systolic arterial blood pressure during LA-BC or when the bladder was distended by a range of pressures. In normal rats, KW-7158 (10 and 100 microg/kg, i.v.) did not alter the amplitude or volume threshold for inducing LA-BC but increased the intercontraction interval. After xylene-irritation, which decreased volume threshold and intercontraction interval and induced small amplitude bladder contractions, KW-7158 increased volume threshold (65%) and intercontraction interval (150%) and decreased the number of small amplitude bladder contractions. Vesico-vascular reflexes induced during LA-BC or by bladder distension were suppressed (19.4-100%) by KW-7158. The effect of KW-7158 to depress vesico-vascular reflexes as well as xylene-induced bladder hyperactivity without altering the amplitude of contractions is consistent with the view that the drug affects reflex bladder activity at least in part by depressing afferent pathways.
Lu
Shing-Hwa
SH
Department of Pharmacology, University of Pittsburgh School of Medicine, E1303A, Biomedical Science Tower, 200 Lothrop St., Pittsburgh, PA 15261, USA. shinghwa@pitt.edu
Yamagata
Tsuyoshi
T
Atsuki
Kaoru
K
Sun
Lushen
L
Smith
Christopher P
CP
Yoshimura
Naoki
N
Chancellor
Michael B
MB
de Groat
William C
WC
D000818:Animals; D001582:Benzothiepins / Q000494:pharmacology*; D001794:Blood Pressure / Q000502:physiology*; D005260:Female; D007509:Irritants / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012018:Reflex / Q000187:drug effects*; D013599:Systole; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D001745:Urinary Bladder Diseases / Q000139:chemically induced / Q000503:physiopathology; D014992:Xylenes / Q000494:pharmacology
D001582:Benzothiepins; D007509:Irritants; D014992:Xylenes; C466985:KW 7158