{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T11:57:11Z","timestamp":1784030231027,"version":"3.55.0"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2003,2,10]],"date-time":"2003-02-10T00:00:00Z","timestamp":1044835200000},"content-version":"vor","delay-in-days":40,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurourology and Urodynamics"],"published-print":{"date-parts":[[2003,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>To compare in vivo the efficacy, potency, and bladder\u2013vascular selectivity of ATP\u2010sensitive potassium channel openers (KCOs), YM934 and (\u2010)\u2010cromakalim to a muscarinic antagonist, tolterodine in a novel partial outlet obstructed pig model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Partially obstructed female Landrace pigs were implanted with telemetry transmitters to allow the continuous measurement of intravesical, abdominal and arterial pressures. A subcutaneous port catheter was used to adjust bladder volume. Bladder and arterial pressure were simultaneously monitored under isoflurane anesthesia before and after increasing i.v. doses of test compounds.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Under anesthesia, voiding was completely inhibited, but spontaneous, nonvoiding bladder contractions were observed with mean amplitude of 16\u2009\u00b1\u20091 cm H<jats:sub>2<\/jats:sub>O, duration of 35\u2009\u00b1\u20092 seconds, and intercontraction interval of 43\u2009\u00b1\u20094 seconds (n\u2009=\u200925). YM934 and (\u2010)\u2010cromakalim both caused dose\u2010dependent decreases in bladder contraction area under the curve (AUC) with effective doses to inhibit AUC by 35% of 3.6 and 14.9 nmol\/kg, i.v., respectively. However, concomitant reductions in mean arterial pressure of 12 and 13% were also observed. Tolterodine did not inhibit spontaneous bladder contractions at doses up to 100 nmol\/kg, i.v. corresponding to plasma concentrations up to 41 ng\/mL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The superior efficacy of KCOs to inhibit spontaneous bladder contractions relative to tolterodine support the hypothesis that KCOs may provide an alternate therapeutic mechanism to treat symptoms of overactive bladder if bladder\u2010vascular selectivity can be sufficiently improved. The minimally invasive model described herein appears useful in the preclinical evaluation of potential therapeutics targeted to treat the overactive bladder. Neurourol. Urodynam. 22:147\u2013155, 2003. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/nau.10103","type":"journal-article","created":{"date-parts":[[2003,2,11]],"date-time":"2003-02-11T16:30:21Z","timestamp":1044981021000},"page":"147-155","source":"Crossref","is-referenced-by-count":18,"title":["Effects of ATP\u2010sensitive K<sup>+<\/sup> channel openers and tolterodine on involuntary bladder contractions in a pig model of partial bladder outlet obstruction"],"prefix":"10.1002","volume":"22","author":[{"given":"Thomas A.","family":"Fey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murali","family":"Gopalakrishnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James G.","family":"Strake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda L.","family":"King","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge D.","family":"Brioni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P.","family":"Sullivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Coghlan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Brune","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,2,10]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-4295(97)00595-5"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(00)00388-5"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1998.tb04376.x"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.3109\/00498258909034680"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-410x.1999.00101.x"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm000484"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(88)90238-6"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)40785-3"},{"key":"e_1_2_1_10_1","first-page":"136","article-title":"The pharmacokinetics of cromakalim, BRL 34915, a new antihypertensive agent, in healthy male subjects","volume":"25","author":"Davies BE","year":"1987","journal-title":"Br J Clin Pharmacol"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.1989.tb06048.x"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199011000-00015"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1991.tb12233.x"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-410X.2003.03069.x"},{"key":"e_1_2_1_15_1","first-page":"37","article-title":"Effects of KATP channel openers (KCOs) and tolterodine on unstable bladder contractions in an improved model of partial outlet obstruction in pigs","volume":"165","author":"Fey TA","year":"2001","journal-title":"J Urol"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.1989.tb05191.x"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199903000-00023"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-3623(97)00437-0"},{"key":"e_1_2_1_19_1","first-page":"884","article-title":"Zeneca ZD6169: a novel KATP channel opener with in vivo selectivity for urinary bladder","volume":"274","author":"Howe BB","year":"1995","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1992.tb09440.x"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)40633-1"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)39012-2"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-410X.1997.00257.x"},{"key":"e_1_2_1_24_1","first-page":"S62","article-title":"Cost effectiveness and quality of life considerations in the treatment of patients with overactive bladder","volume":"7","author":"McGhan WF","year":"2001","journal-title":"Am J Manag Care"},{"key":"e_1_2_1_25_1","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0022-5347(17)65296-0","article-title":"Experimental studies of ureteral peristaltic patterns in the pig. 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