Effects of sildenafil on erectile activity in mice lacking neuronal or endothelial nitric oxide synthase

被引:48
|
作者
Cashen, DE [1 ]
MacIntyre, DE [1 ]
Martin, WJ [1 ]
机构
[1] Merck Res Labs, Dept Pharmacol, Rahway, NJ 07065 USA
关键词
cavernous nerve; electrical stimulation; erectile function; nitric oxide synthase; phosphodiesterase inhibitors; sildenafil;
D O I
10.1038/sj.bjp.0704772
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 Using an in vivo model of erectile activity, the effects of sildenafil were studied in mice lacking neuronal or endothelial nitric oxide synthase (nNOS and eNOS, respectively). 2 Under pentobarbitone anaesthesia, intracavernous pressure (ICP) and mean arterial pressure (MAP) were monitored continuously in wild-type, nNOS-/- and eNOS-/- mice. The magnitude of erectile activity was quantified as the ratio of ICP to MAP. 3 No differences in basal ICP or MAP were observed amongst wild-type, eNOS-/- and nNOS-/- mice. Electrical stimulation of the cavernous nerve (ESCN; 4.0 V, 16 Hz, 1 ms, 30 s) evoked increases in ICP and ICP/MAP as well as penile tumescence. Responses to ESCN were reduced in nNOS-/-, but not in eNOS-/- mice. 4 L-NAME (50 mg kg(-1), i.v.) significantly increased MAP and attenuated erectile responses in both wild-type and eNOS-/- mice. 5 Sildenafil (I mg kg(-1), i.v.) augmented electrically-evoked erectile activity in a voltage-dependent manner in wild-type mice and facilitated erectile responses in eNOS-/- mice. By contrast, sildenafil failed to augment the diminished erectile responses in mice lacking the nNOS isoform. 6 These data reveal the relative importance of nNOS, compared to eNOS, as the critical NOS isoform in the control of erectile function and illustrate that the nNOS isoform is required for sildenafil-induced facilitation of erectile responses in vivo in mice.
引用
收藏
页码:693 / 700
页数:8
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