Inhibition of Phosphodiesterase 4 Enhances Clitoral and Vaginal Blood Flow Responses to Dorsal Clitoral Nerve Stimulation or PGE1 in Anesthetized Female Rats

被引:9
作者
Castiglione, Fabio [1 ,2 ]
Bergamini, Alice [1 ]
Russo, Andrea [1 ,2 ]
La Croce, Giovanni [1 ]
Castagna, Giulia [1 ]
Colciago, Giorgia [1 ]
Salonia, Andrea [1 ]
Rigatti, Patrizio [1 ]
Montorsi, Francesco [1 ]
Hedlund, Petter [1 ,2 ,3 ]
机构
[1] Hosp San Raffaele, Dept Urol, Urol Res Inst, I-20132 Milan, Italy
[2] Lund Univ, Dept Clin Pharmacol, Lund, Sweden
[3] Linkoping Univ, Dept Clin Pharmacol, Linkoping, Sweden
基金
英国医学研究理事会;
关键词
Blood Flow; Clitoris; Vagina; Doppler; PDE4; cAMP; VIP; VASOACTIVE INTESTINAL POLYPEPTIDE; OXIDE SYNTHASE ISOFORMS; GENITAL SEXUAL AROUSAL; NITRIC-OXIDE; CYCLIC-GMP; CORPUS CAVERNOSUM; SIGNALING PATHWAY; IN-VITRO; RABBIT; EXPRESSION;
D O I
10.1111/jsm.12058
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Introduction. Cyclic adenosine 35 monophosphate (cAMP) is produced by adenylate cyclase after activation by, e.g., vasoactive intestinal polypeptide or prostaglandin E1 (PGE1). The cAMP-degrading phosphodiesterase 4 (PDE4) is expressed in the vagina and clitoris, but no information is available on the functional role for PDE4-related signals in the female neurovascular genital response. Aim. The aim of this study is to study the effect of inhibition of PDE4 with rolipram on nerve- and PGE1-induced vaginal and clitoral blood flow responses of rat. Methods. Measure of clitoral and vaginal blood flow and blood pressure in anesthetized rats during activation of the dorsal clitoral nerve (DCN) before and after intraperitoneal administration of rolipram or sildenafil (phosphodiesterase type 5 inhibitors [PDE5]) and nitro-L-arginine (L-NNA) (nitric oxide synthase inhibitor). Effect by topical administration of PGE1 on genital blood flow was also evaluated. Main Outcome Measure. Blood flow was recorded as tissue perfusion units (TPU) by a Laser Doppler Flowmeter. Mean arterial blood pressure (MAP) was recorded (cmH2O) in the carotid artery. Blood flow responses are expressed as TPU/MAP. Unpaired t-test and an analysis of variance were used. Results. Compared with control stimulations, rolipram (0.3mg/kg) caused a twofold increase in peak blood flow (P<0.05) and fourfold increase of the rate of clitoral blood flow during activation of the DCN (P<0.05). Simultaneously, a twofold increase in peak blood flow and threefold increase in rate of blood flow were noted in the vagina (P<0.05). Similar effects were noted for sildenafil (0.2mg/kg) (P<0.05). Inhibitory effects by L-NNA (60mg/kg) on blood flow responses to DCN activation were significantly lower for rats treated with rolipram than with sildenafil (P<0.05). PGE1-induced (10g) blood flow responses were significantly higher (P<0.05) in rats treated with rolipram than with sildenafil. Conclusions. These findings suggest that the cAMP/PDE4 system may be of similar functional importance as the nitric oxide/cyclic guanosine monophosphate/PDE5 pathway for neurovascular genital responses of the female rat. Castiglione F, Bergamini A, Russo A, La Croce G, Castagna G, Colciago G, Salonia A, Rigatti P, Montorsi F, and Hedlund P. Inhibition of phosphodiesterase 4 enhances clitoral and vaginal blood flow responses to dorsal clitoral nerve stimulation or PGE1 in anesthetized female rats. J Sex Med 2013; 10: 939-950.
引用
收藏
页码:939 / 950
页数:12
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