Topical administration of a novel nitric oxide donor, linear polyethylenimine-nitric oxide/nucleophile adduct (DS1), selectively increases vaginal blood flow in anesthetized rats.
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 191+/-24, 226+/-22 and 166+/-23% 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.
Pacher
P
P
Inotek Pharmaceuticals Corporation, Beverly, Massachusetts 01915, USA. ppacher@hotmail.com
Mabley
J G
JG
Liaudet
L
L
Evgenov
O V
OV
Southan
G J
GJ
Abdelkarim
G E
GE
Szabó
C
C
Salzman
A L
AL
D000287:Administration, Topical; D000758:Anesthesia; D000818:Animals; D005260:Female; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000494:pharmacology*; D011094:Polyethyleneimine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects*; D014621:Vagina / Q000098:blood supply*
D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; C470091:linear polyethylenimine-NONOate; D011094:Polyethyleneimine