Urological Research Institute, Department of Urology, San Raffaele Hospital, Via Olgettina 58, Milan, Italy.
J Sex Med. 2013 Apr;10(4):939-50. doi: 10.1111/jsm.12058. Epub 2013 Jan 24.
INTRODUCTION.: Cyclic adenosine 3'5' 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 (cmH2 O) 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 (0.3 mg/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 (0.2 mg/kg) (P < 0.05). Inhibitory effects by L-NNA (60 mg/kg) on blood flow responses to DCN activation were significantly lower for rats treated with rolipram than with sildenafil (P < 0.05). PGE1-induced (10 μg) 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.
环磷酸腺苷（cAMP）由腺苷酸环化酶产生，在被血管活性肠多肽或前列腺素 E1（PGE1）等激活后产生。cAMP 降解磷酸二酯酶 4（PDE4）在阴道和阴蒂中表达，但尚无关于 PDE4 相关信号在女性神经血管生殖器反应中的功能作用的信息。目的：本研究旨在研究用罗利普兰抑制 PDE4 对大鼠阴部神经（DCN）和 PGE1 诱导的阴道和阴蒂血流反应的影响。方法：在给予 rolipram 或西地那非（磷酸二酯酶 5 抑制剂[PDE5]）和硝基-L-精氨酸（L-NNA）（一氧化氮合酶抑制剂）后，在麻醉大鼠中测量背侧阴蒂神经（DCN）激活前后的阴蒂和阴道血流和血压，并评估 PGE1 对生殖器血流的局部作用。主要观察指标：血流通过激光多普勒血流计记录为组织灌注单位（TPU）。颈动脉记录平均动脉血压（MAP）（cmH2 O）。血流反应表示为 TPU/MAP。使用未配对 t 检验和方差分析。结果：与对照刺激相比，rolipram（0.3mg/kg）引起峰值血流增加两倍（P<0.05），DCN 激活时阴蒂血流增加四倍（P<0.05）。同时，阴道中也观察到峰值血流增加两倍，血流速度增加三倍（P<0.05）。西地那非（0.2mg/kg）也有类似的作用（P<0.05）。用 L-NNA（60mg/kg）抑制 DCN 激活引起的血流反应，rolipram 处理的大鼠比用西地那非处理的大鼠明显降低（P<0.05）。用 rolipram 处理的大鼠的 PGE1 诱导（10μg）血流反应明显高于用西地那非处理的大鼠（P<0.05）。结论：这些发现表明，cAMP/PDE4 系统对于雌性大鼠的神经血管生殖器反应可能具有与一氧化氮/环鸟苷单磷酸/PDE5 途径相似的功能重要性。
