PHARMACOLOGICAL ANALYSIS OF THE LOCAL AND REFLEX RESPONSES TO BRADYKININ ON RAT URINARY-BLADDER MOTILITY IN-VIVO

1 The topical application of bradykinin (BK) (0.05-5000 pmol/rat) onto the serosal surface of the urinary bladder in urethane-anaesthetized rats, evoked low amplitude tonic contractions (not exceeding 25 mmHg) or high amplitude (about 50 mmHg), phasic reflex contractions (chemoce ptive micturition reflex) which were abolished by bilateral ablation o f the pelvic ganglia. In ganglionectomized rats, BK induced only a loc al, tonic-type contraction. 2 Systemic capsaicin pretreatment (164 mu mol kg(-1), 4 days before) reduced the incidence of chemoceptive refle x induced by BK (500 pmol/rat) but had no effect on the magnitude of t he tonic-type contraction elicited by BK in ganglionectomized rats. In domethacin (11 mu mol kg(-1), 20 min before) reduced the incidence but not the amplitude of the reflex contractions induced by topical appli cation of BK (500 pmol/rat). In ganglionectomized rats, indomethacin ( 11 mu mol kg(-1), 20 min before) decreased the amplitude of the tonic contraction evoked by BK. Indomethacin did not affect the chemoceptive reflex induced by topical application of capsaicin (15 nmol/rat) onto the bladder. 3 Intrathecal administration of the tachykinin NK, recep tor antagonists, RP 67,580 (10 nmol/rat) or SR 140,333 (10 nmol/rat), abolished the chemoceptive reflex induced by BK without modifying the magnitude of the tonic contraction. SR 140,333 (10 nmol/rat) also abol ished the occurrence of the chemoceptive reflex induced by capsaicin. 4 Intravenous administration of the B-2 receptor antagonist, Hoe 140 ( 35 nmol kg(-1), 10 min before) abolished the reflex and local effects induced by BK on bladder motility but failed to modify the chemoceptiv e reflex induced by topical application of capsaicin (15 nmol/rat). 5 Intrathecal administration of Hoe 140 (10 nmol/rat) reduced the incide nce of the chemoceptive reflex induced by BK but had no effect on the amplitude of the local motor response. Likewise, Hoe 140 (10 nmol/rat, i.t.) reduced the incidence of reflex bladder contractions induced by topical application of capsaicin (15 nmol/rat) without affecting the magnitude of the tonic-type contraction. 6 These findings indicate tha t BK stimulates motility through B-2 receptors in the rat urinary blad der. BK activates the reflex response by stimulating capsaicin-sensiti ve afferent nerves with a contribution from prostanoids. At the spinal cord level, tachykinin NK1 and BK B-2 receptors could also be involve d in the chemoceptive reflex induced by BK or capsaicin.