Response of rabbit detrusor muscle to bradykinin

doi:10.1016/0024-3205(81)90123-5

Life Sciences

Volume 28, Issue 6, 9 February 1981, Pages 603-608

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Abstract

The contractile response to bradykinin was studied in isolated longitudinal strips of detrusor muscle from rabbit urinary bladder. Strips responded slowly with contractions which were comparable in magnitude to acetylcholine but much greater than those produced by arachidonic acid. The bradykinin dose-response curve was very shallow (Clark's ratio = 10⁻⁵), with an ED50 of 0.2 μM. Bradykinin-induced contractions were unaffected by 0.4 μM atropine or 0.2 μM eserine. This suggests, in contrast to reports on rat bladder, that acetylcholine release does not contribute to the response. However, pretreatment with 10 μM naproxen antagonized bradykinin-induced contractions without affecting acetylcholine. It is concluded that, as in many other tissues, in the urinary bladder at least part of the response to bradykinin is mediated through prostaglandins. Bradykinin probably also has a direct action since higher concentrations are less susceptible to naproxen, and it produces a much greater contraction than the maximum achievable with arachidonic acid.

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Up-regulation of bradykinin response in rat and human bladder smooth muscle
2000, Journal of Urology
Responses to bradykinin were investigated in vitro in isolated control and hypertrophic smooth muscle strips from rat bladder.
Bladder hypertrophy was induced by a 10-day period of partial urinary outflow obstruction. In addition, human bladder strips were also investigated.
Bradykinin (1 nM. to 1 μM.) caused contractions in all tissues studied. In the freshly isolated rat bladder preparations bradykinin induced contractions were similar and of small amplitude in control and hypertrophic tissues. After a 4-hour equilibratory period contractile responses to bradykinin and the B1 specific bradykinin receptor agonist desArg⁹ bradykinin were slightly increased in the controls but there was approximately a 6-fold increase in the hypertrophic muscle strips. After 4 hours of equilibration the human bladder strips showed a smaller but still significant increase in contractile response to bradykinin. Indomethacin, a cyclooxygenase inhibitor, almost abolished the increased response, which suggests that prostanoids are involved in the up-regulated response. The protein synthesis inhibitor cycloheximide inhibited up-regulation by approximately 50% in hypertrophic and control muscle strips from rat bladder and normal muscle from human bladder.
These results demonstrate that bradykinin receptor responses are present in rat and human detrusor muscle and they can be up-regulated in vitro. Experiments on hypertrophic rat bladder revealed that this process is enhanced in hypertrophy.
Potentiation by bradykinin and substance P of purinergic neurotransmission in urinary bladder
1996, Journal of Urology
The higher than normal levels of substance P (SP) and the kinins in patients suffering from interstitial cystitis suggest that they may contribute to the complex symptoms of the condition. The purpose of our experiments was to determine whether SP and bradykinin (BK) influence the excitatory motor innervation of the urinary bladder.
Strips of guinea pig urinary bladder were placed in isolated tissue baths, and the influence of SP and BK on contractions induced by transmural electrical stimulation and cholinergic and purinergic agonists was evaluated.
Substance P and BK potentiated responses to the purinergic component of the neurogenic stimulation (that part of the contractile response that remains after treatment with atropine) and potentiated responses to exogenously applied adenosine triphosphate (ATP). The peptides did not potentiate the response to the cholinergic component of the nerve-induced contraction (that part of the neurogenic response that remains after desensitization of purinoceptors with alpha, beta-methylene ATP) nor responses to carbachol. The potentiating actions of SP and BK were reduced but not abolished by treatment with meclofenamic acid.
Substance P and BK potentiate the neurogenic response of the bladder by influencing the purinergic component of the excitatory motor innervation, apparently at a postjunctional site. Prostaglandins may be involved in mediating some of the actions of these peptides.
Blockade of kinin-induced responses of the guinea-pig isolated urinary bladder by the extract of Mandevilla velutina
1990, General Pharmacology
- 1.
  1. The crude extract (CE) from M. velutina (0.2–0.8 mg/ml), antagonized in a dose-dependent and reversible manner bradykinin (BK)- and lysyl-BK-induced contractions of the guinea-pig urinary bladder in vitro.
- 2.
  2. Schild plots yielded nominal pA₂ values (as g/ml) of 3.5 and 3.7, but the slopes were significantly greater than unity.
- 3.
  3. At concentrations 2–10-fold higher, the CE failed to affect responses to acetylcholine or histamine.
- 4.
  4. In electrically-stimulated tissue, BK, L-BK and M-L-BK potentiated nerve-mediated twitch responses and increased muscular tone. The B₁ agonist [des-Arg⁹]-BK, was inactive up to 10 μM.
- 5.
  5. The CE from M. velutina (0.4 mg/ml) inhibited both actions of the kinins.
Bradykinin-induced contractions of canine prostate and bladder: Effect of angiotensin-converting enzyme inhibition
1990, Journal of Urology
Alpha-adrenergic, cholinergic, and serotonergic receptor-mediated contractile responses have been well characterized in the genitourinary tissues of several mammalian species. The present study characterizes the in vitro contractile responsiveness of canine bladder and prostate to the peptides, bradykinin, angiotensin I, and angiotensin II. All preparations contracted to 0.15 M KCl. Bradykinin elicited contractile responses in both prostate (10⁻¹⁰ to 10⁻⁷ M) and bladder (10⁻¹⁰ to 10⁻⁶ M). In both tissues, angiotensin II produced minimal responses and angiotensin I failed to elicit contractions. The potent angiotensin converting enzyme (ACE) inhibitor, enalaprilic acid [MK-422] (10⁻⁶ M) increased the contractile response of the prostate to bradykinin two-fold while having no effect on bradykinin-induced contractions in the bladder. Enalaprilic acid did not affect the contractile responses of the two tissues to angiotensin I or angiotensin II. The canine urogenital tissue contractile responses to bradykinin, angiotensin I, and angiotensin II may have relevance to human physiology. Previous studies have demonstrated that human prostatic tissue, specifically benign prostatic hyperplasia (BPH), has the highest concentration of ACE activity of tissues evaluated. Bradykinin is a potent peptidergic contractile agent in canine bladder and prostate. The activity of enalaprilic acid to amplify the bradykinin-induced contractions in the canine prostate is consistent with high levels of ACE in the tissue. These data confirm the sensitivity of the canine prostate to bradykinin and report for the first time, the ability of bradykinin to induce contractions in the prostate. These studies support the possibility that bradykinin may be involved in mediating micturition under normal and pathological states such as infravesical obstruction secondary to BPH. Furthermore, the results from these investigations in canine urogenital tissues, if applicable to humans, suggest that urinary function be closely monitored in patients receiving ACE inhibitor therapy. (J. Urol, 144: 390-392, 1990)
A study of the atropine-resistant component of the neurogenic response of the rabbit urinary bladder
1984, European Journal of Pharmacology
Rabbit bladder body was stimulated to contract by a number of agonists, of which bradykinin was the most potent, and ATP one of the least potent substances tested. The atropine-resistant component of the neurogenic response was unaffected by 2 × 10⁻⁵ M chlorpheniramine or 10⁻⁶ M methysergide, doses which suppressed responses to histamine or 5HT. Indomethacin 10⁻⁵ M or 10⁻⁵ M capsaicin both reduced the atropine-resistant component. Following treatment with 10⁻⁶ M atropine and 10⁻⁵ M prazosin, 10⁻⁴ M ANAPP₃ produced a further suppression of the response, but did not antagonize the response to ATP. In the bladder body, the transmitter(s) responsible for the neurogenic response may be acetylcholine and prostaglandins and possibly ATP and substance P.

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Response of rabbit detrusor muscle to bradykinin

Abstract

Eur. J. Pharmac.

Prostaglandins

Prostaglandins

Prostaglandins

A. Rev. Pharmac.

Br. J. Pharmac.

J. Pharmac. Exp. Ther.

Br. J. Pharmac.

Br. J. Pharmac.

J. Pharmac. Exp. Ther.