ROLE OF INTRATHECAL TACHYKININS FOR MICTURITION IN UNANESTHETIZED RATS WITH AND WITHOUT BLADDER OUTLET OBSTRUCTION

1 The effects on micturition of RP 67,580, a selective NK1 receptor an tagonist, and SR 48,968, a highly potent antagonist at NK2 receptor si tes, given intrathecally (i.t.) or intra-arterially (i.a.) near the bl adder, were investigated in unanaesthetized rats with and without blad der outlet obstruction. 2 In normal rats, RP 67,580, given i.t. in dos es of 2 and 20 nmol per rat, decreased micturition pressure, but did n ot change other cystometric parameters. After 20 nmol of RP 67,580, dr ibbling incontinence due to retention was observed in 1 out of 7 anima ls. This effect was reversible. I.t. RP 67,580 in a dose of 2 nmol, ha d no effect on hyperactivity induced by intravesically instilled capsa icin. 3 In animals with bladder hypertrophy secondary to outflow obstr uction, RP 67,580, given i.t. in a dose of 2 nmol per rat, decreased t he micturiton pressure, but had no effect on other cystometric paramet ers. After 20 nmol, dribbling incontinence due to retention was observ ed in 5 out of 7 animals. 4 RP 67,580, given i.a. in a dose of 4 nmol, had little effect on the cystometric parameters investigated, both in normal animals and rats with bladder hypertrophy. 5 SR 48,968, given i.t. in doses of 2 and 20 nmol per rat, had no clear-cut effects on th e micturition pattern in normal rats, or rats with bladder hypertrophy . However, the drug reduced capsaicin-induced bladder hyperactivity. W hen given i.a. in a dose of 4 nmol, SR 48,968 had no effect on cystome tric parameters in normal rats or rats with bladder hypertrophy. 6 The effects of both RP 67,580 and SR 48,968 were stereoselective, their e nantiomers (RP 68,651 and SR 48,965) being inactive. 7 These results t hus suggest that at the spinal level there is a tachykinin involvement (via NK1 receptors) in the micturition reflex induced by bladder fill ing, both in normal rats, and, more clearly, in animals with bladder h ypertrophy secondary to outflow obstruction. The bladder response to f illing was not influenced by blockade of vesical NK1 and NK2 receptors . Oh the other hand, the bladder hyperactivity evoked by intravesical capsaicin seems to involve NK2 receptors both at the bladder and spina l levels.