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Titolo:
Effect of intravesical nitric oxide therapy on cyclophosphamide-induced cystitis
Autore:
Ozawa, H; Chancellor, NB; Jung, SY; Yokoyama, T; Fraser, MO; Yu, YB; De Groat, WC; Yoshimura, N;
Indirizzi:
Univ Pittsburgh, Sch Med, Div Urol Surg, Pittsburgh, PA 15213 USA Univ Pittsburgh Pittsburgh PA USA 15213 ol Surg, Pittsburgh, PA 15213 USA Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15213 USA Univ Pittsburgh Pittsburgh PA USA 15213 armacol, Pittsburgh, PA 15213 USA
Titolo Testata:
JOURNAL OF UROLOGY
fascicolo: 6, volume: 162, anno: 1999,
pagine: 2211 - 2216
SICI:
0022-5347(199912)162:6<2211:EOINOT>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
INDUCED HEMORRHAGIC CYSTITIS; BLADDER IRRITATION; URINARY-BLADDER; C-FOS; RATS; PHARMACOLOGY; INVOLVEMENT; EXPRESSION; AFFERENT; NEURONS;
Keywords:
nitric oxide; cyclophosphamide; urinary bladder; inflammation; detrusor hyperactivity; bladder afferent neurons;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Ozawa, H Univ Pittsburgh, Sch Med, Div Urol Surg, Suite 700,Kaufmann Bldg,3471 5th Ave, Pittsburgh, PA 15213 USA Univ Pittsburgh Suite 700,Kaufmann Bldg,3471 5th Ave Pittsburgh PA USA 15213
Citazione:
H. Ozawa et al., "Effect of intravesical nitric oxide therapy on cyclophosphamide-induced cystitis", J UROL, 162(6), 1999, pp. 2211-2216

Abstract

Purpose: This study was conducted to examine effects of nitric oxide (NO) donors on bladder hyperactivity induced by cyclophosphamide (CYP)-induced cystitis. Materials and Methods: Female Sprague-Dawley rats received a single intraperitoneal injection of CYP (100 mg./kg.), and then their micturition pattern including mean micturition volume and the number of micturitions during 24 hours was recorded in a metabolic cage before and after CYP treatment. Forty-eight hours after CYP injection, bladder function under urethane anesthesia was evaluated by cystometry with continuous saline infusion (0.04 mi. per minute) or under isovolumetric conditions (0.8 mi. bladder volume). NO donors, S-nitroso-N-acetyl-penicillamine (SNAP, 2 mM) or sodium nitroprusside (SNP, 1 mM), and an NO synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME, 20 mM) were administered intravesically. Direct action ofSNAP on bladder afferent neurons was also tested in a patch-clamp recording study. Results: The number of micturitions significantly increased during the first 24 hours after CYP injection (19.0 +/- 0.88 versus 92.1 +/- 16.3 micturitions/24 hours, mean +/- SE, n = 25) (p <0.001). There was no significant difference in total micturition volume before (12.3 +/- 1.0 ml./24 hours) and after CYP treatment (15.6 +/- 1.5 ml./24 hours). During continuous infusion cystometry, intercontraction interval (ICI) was smaller in CYP-injected rats than in control rats. In CYP-injected animals, NO donors increased theICI, but did not change the amplitude of bladder contractions. Continuous intravesical infusion of the NOS inhibitor did not alter the cystometric parameters. During cystometry under isovolumetric conditions, contraction frequency was decreased after NO donor administration. NO donors did not influence bladder activity in control rats. Ln patch clamp recordings, when SNAP(500 mu M was directly applied to dissociated afferent neurons innervatingthe urinary bladder, high-voltage-activated Ca channel currents were suppressed by approximately 30%. Conclusions: Intravesical NO donors can suppress CYP-induced bladder hyperactivity. We hypothesize that the effect of NO donors is not due to smooth muscle relaxation, but rather due to an inhibitory effect on bladder afferent pathways that was manifested by an increase in intercontraction intervalwithout changes in contraction amplitude. NO donors may be considered as apossible treatment of CYP-induced and other types of bladder inflammation.

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Documento generato il 03/04/20 alle ore 20:35:59