Short Communication

International Journal of Impotence Research (2003) 15, 461–464. doi:10.1038/sj.ijir.3901045

Topical administration of a novel nitric oxide donor, linear polyethylenimine-nitric oxide/nucleophile adduct (DS1), selectively increases vaginal blood flow in anesthetized rats

This study was supported by the National Institutes of Health (Grant R43HD41288).

P Pacher1,2, JG Mabley1, L Liaudet1, OV Evgenov1, GJ Southan1, GE Abdelkarim1, C Szabó1 and AL Salzman1

1Inotek Pharmaceuticals Corporation, Beverly, Massachusetts, USA

Correspondence: P Pacher, MD, PhD, Inotek Corporation, Suite 419E, 100 Cummings Center, Beverly, MA 01915, USA. E-mail: ppacher@hotmail.com

2Present address: NIAAA, Park Bldg., Rm. 445, 12420 Parklawn Drive, MSC-8115 Rockville, MD 20852, USA. E-mail: pacher@mail.nih.gov

Received 27 August 2002; Revised 1 December 2002; Accepted 5 December 2002.

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Abstract

The aim of the present study was to test the effects of a topical administration of a novel nitric oxide donor, linear polyethylenimine-nitric oxide/nucleophile adduct (DS1), on vaginal blood flow and hemodynamics in rats. Laser Doppler flowmetry was used to measure blood flow changes following topical application of DS1 (0.3 or 1.5 mg in 0.15 ml saline) into the vagina of anesthetized Wistar rats. In vivo hemodynamic parameters were measured with Millar-tip-catheter placed in the left ventricle. DS1 (1.5 mg) increased vaginal blood flow by 191plusminus24, 226plusminus22 and 166plusminus23% of the baseline value (at 5, 15 and 30 min, respectively, after application) without affecting systemic blood pressure, heart rate and cardiac function. The increased vaginal blood flow following DS1 application returned to baseline between 45 and 60 min. Thus, topical application of nitric oxide donors such as DS1 may be useful for the treatment of female sexual dysfunction that develops due to an impairment of local blood flow supply to the vaginal tissue.

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