Effect of Intravesical Nitric Oxide Therapy on Cyclophosphamide-Induced Cystitis

Ozawa, Hideo; Chancellor, Michael B.; Jung, Sukyoung; Yokoyama, Teruhiko; Fraser, Matthew O.; Yu, Yongbei; Groat, William C. de; Yoshimura, Naoki

doi:10.1016/s0022-5347(05)68161-x

Cited by 125 publications

(87 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…24,25) Moreover, it was reported that endogenous and exogenous NO had inhibitory effects on the sensory afferent nerve activity in the bladder when the bladder was irritated by treatment with cyclophosphamide 7) or capsaicin in rat. 26) These studies support that NO plays physiological and pathophysiological roles in not only the relaxation of the urethra and urethral sphincter during micturition leading to decrease in urinary resistance during the emptying phase, but the suppression of afferent nerve function in the bladder, so that a bladder selective NO-donor without cardiovascular effects may be one of possible targets for medical treatment of LUTS.…”

Section: Discussionsupporting

confidence: 54%

Nicorandil, a Potassium Channel Opener and Nitric Oxide Donor, Improves the Frequent Urination without Changing the Blood Pressure in Rats with Partial Bladder Outlet Obstruction

Sudo

Ishizuka

Otsuka

et al. 2008

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

With advance of an aged society, the populations with lower urinary tract symptoms (LUTS) are increasing. These symptoms can divide into problems with storage (urinary frequent urination, nocturia and urgency) and emptying (incomplete emptying and development of urinary retention). The frequent urination is one of severe urological symptoms caused by the lower urinary tract dysfunction such as overactive bladder (OAB) and benign prostatic hyperplasia (BPH) resulting in bladder outlet obstruction (BOO). Antimuscarinics are the first line treatment at present and show symptom improvement in many patients with frequent urination 1) but are limited by side effects such as dry mouth, blurred vision, constipation and urinary retention in some patients, resulting in a significant level of noncompliance. Therefore, there are substantial unmet medical needs for novel or more effective agents compared with antimuscarinics. Currently, a number of drugs with a variety of mechanisms are in development.ATP-sensitive potassium channel openers (KCO) and nitric oxide (NO) donors have been possible candidates with novel mechanism for the treatment of frequent urination. Opening the potassium channel in bladder smooth muscles evokes membrane hyperpolarization which reduces calcium influx via a voltage-dependent calcium channel and relaxes the detrusor smooth muscle. Expression of ATP-sensitive potassium channel has been detected in bladder from several species including human and rat.2) KCO such as pinacidil and cromakalim have been shown to inhibit isolated bladder contractions in several species, including humans.3-5) Although cromakalim causes an increase in micturition interval in rats, blood pressure was reduced at the same dose.6) On the other hand, the important action of NO on outflow regions appears to be widely accepted.2) Masuda et al. reported that endogenous and exogenous NO depresses reflex bladder activity by suppressing the excitability and/or release of transmitters from bladder afferent nerves in tests using overactivity of the detrusor induced by capsaicin. 7) Thus, we postulated that a drug that possesses nitrate activity in addition to KCO activity, as well as the bladder selective characteristics, would be more useful in the treatment of frequent urination than a pure KCO.Nicorandil (2-nicotinamidoethyl-nitrate ester), which has been used clinically as treatment for angina and acute heart failure, is a KCO that donates NO. Nicorandil is known to improve coronary circulation without changing the systemic blood pressure in humans.8) The pharmacological effects of nicorandil on frequent urination in three different OAB models in rat were reported recently.9) This study was conducted to confirm whether nicorandil could improve the frequent urination symptom without changing the blood pressure using the BOO rat model, compared with those of a pure KCO, cromakalim and a NO donor, isosorbide dinitrate (ISDN). MATERIALS AND METHODSTests were conducted on female SD rats (140-200 g, Japan SLC, Inc., Shizuoka, Japan). A...

show abstract

Section: Discussionsupporting

confidence: 54%

Nicorandil, a Potassium Channel Opener and Nitric Oxide Donor, Improves the Frequent Urination without Changing the Blood Pressure in Rats with Partial Bladder Outlet Obstruction

Sudo

Ishizuka

Otsuka

et al. 2008

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…76 For example, intravesical administration of NO donors suppresses the bladder hyperactivity in animals treated with cyclophosphamide. 77,78 In addition, it has been reported that NO levels are decreased in patients with interstitial cystitis, a clinical syndrome that is characterized by bladder pain, urinary urgency and frequency. 79 Alterations in NO levels could, therefore, affect the excitability of sensory fibers in the urinary bladder.…”

Section: Nitric Oxidementioning

confidence: 99%

Mechanisms of Disease: involvement of the urothelium in bladder dysfunction

2007

View full text Add to dashboard Cite

SUMMARYAlthough the urinary bladder urothelium has classically been thought of as a passive barrier to ions and solutes, a number of novel properties have been recently attributed to urothelial cells. Studies have revealed that the urothelium is involved in sensory mechanisms (i.e. the ability to express a number of sensor molecules or respond to thermal, mechanical and chemical stimuli) and can release chemical mediators. Localization of afferent nerves next to the urothelium suggests that urothelial cells could be targets for neurotransmitters released from bladder nerves or that chemicals released by urothelial cells could alter afferent nerve excitability. Taken together, these and other findings highlighted in this article suggest a sensory function for the urothelium. Elucidation of mechanisms that influence urothelial function might provide insights into the pathology of bladder dysfunction.

show abstract

“…NO released from afferent nerve or urothelium may play a sensory mechanisms in the lower urinary tract. A study of cyclophosphomide-induced cystitis showed that intravesical administration of NO donor depressed bladder hyperactivity [25]. Oral administarion of L-arginine can result in reduced interstitial cystitis symptoms [26].…”

Section: Discussionmentioning

confidence: 99%

The immediate effect of nitric oxide on the rabbit bladder after ovariectomy

Juan¹,

Mannikarottu²,

Schuler³

et al. 2008

Nitric Oxide

View full text Add to dashboard Cite

Ovariectomy resulted in decreased blood flow and hypoxia to the bladder mucosa and smooth muscle. Nitric oxide (NO) played an important role in regulating bladder function during bladder ischemia and reperfusion. This study was designed to evaluate the role of NO on bladder function in the first few days after ovariectomy. Female rabbits were separated into three groups, one which received no medication, pre-medicated with N(omega) -nitro-L-arginine methyl ester (L-NAME) and the third treated with L-arginine. Non-ovariectomized controls and at 1 and 3 days post-ovariectomy, animals from each group were euthanized. Cystometry and in vitro isometric contractile responses were recorded and the oxidative stress markers, nitrotyrosine and protein carbonylation were determined. L-NAME treatment did not significantly alter bladder function after ovariectomy. L-arginine fed, ovariectomized rabbits had lower intravesical pressure and better contractile responses to all forms of stimulation than the ovariectomized rabbits with or without L-NAME. Furthermore, the ovariectomized ones with or without L-NAME had higher oxidative stress markers than L-arginine fed rabbits. This study clearly demonstrates that feeding rabbits with L-arginine can protect the bladder from oxidative free radical damage following short term ovariectomy.

show abstract

Effect of Intravesical Nitric Oxide Therapy on Cyclophosphamide-Induced Cystitis

Cited by 125 publications

References 18 publications

Nicorandil, a Potassium Channel Opener and Nitric Oxide Donor, Improves the Frequent Urination without Changing the Blood Pressure in Rats with Partial Bladder Outlet Obstruction

Nicorandil, a Potassium Channel Opener and Nitric Oxide Donor, Improves the Frequent Urination without Changing the Blood Pressure in Rats with Partial Bladder Outlet Obstruction

Mechanisms of Disease: involvement of the urothelium in bladder dysfunction

The immediate effect of nitric oxide on the rabbit bladder after ovariectomy

Contact Info

Product

Resources

About