Continuous production of endothelium-derived nitric oxide (NO) in peripheral vessels has been shown to modulate vascular resistance and blood pressure. NO is also formed in the brain upon activation of glutamate receptors, which are thought to mediate central autonomic reflexes. In the present study we assessed whether NO plays a role in central autonomic regulation. For this, we have investigated the effects of NG-methyl-L-arginine (NMA), a selective inhibitor of NO synthesis from L-arginine, on sympathetic renal nerve activity (RNA), blood pressure, and heart rate in the anesthetized rat. NMA elicited a dose-dependent sustained increase in blood pressure (approximately 20 and 30 mm Hg, 5 minutes after 10 and 50 mumol/kg i.v., respectively). Heart rate and RNA decreased transiently (15 beats per minute and 40%, respectively); RNA subsequently increased (100%) while blood pressure remained elevated. Baroreceptor deafferentation markedly altered these responses to NMA; the transient decreases in heart rate and RNA were abolished, whereas the increases in RNA and blood pressure were significantly potentiated. After spinal C-1-C-2 transection, there was no increase in RNA, and blood pressure increased to a smaller extent. L-Arginine blocked the NMA-induced increases in blood pressure and RNA. Thus, in addition to modulating vascular resistance by a peripheral action, NO may also play a role in the central regulation of sympathetic tone.

The present study evaluates juvenile stroke-prone spontaneously hypertensive rats (SHRSP) as an animal model of a developmental disorder, which is diagnosed according to hyperactivity-impulsivity and/or inattention. To characterize behavioural alterations, we studied motor activity, as well as emotional and cognitive behaviours in juvenile SHRSP, with and without methylphenidate, a psychostimulant. Ambulatory and rearing activities in the open-field environment were significantly higher in SHRSP than in Wistar-Kyoto rats (WKY). In the elevated plus maze task, the entries into open arms, as an index of impulsivity, were significantly increased in SHRSP. In the Y-maze task, spontaneous alternation behaviour, as an index of attention, was significantly lowered in the male SHRSP, but not in the female SHRSP, indicating that spontaneous alternation deficit is gender specific. Methylphenidate (0.01-1 mg/kg, i.p.) significantly attenuated locomotor hyperactivity at low doses and dose-dependently improved the spontaneous alternation deficit in SHRSP. Our findings reveal that juvenile SHRSP manifest problematic behaviours resembling a developmental disorder, attention-deficit/hyperactivity disorder (ADHD), namely hyperactivity-impulsivity and/or inattention. Methylphenidate alleviated the behavioural symptoms of hyperactivity and inattention. We propose that juvenile SHRSP are an appropriate animal model of a developmental disorder resembling ADHD, from behavioural and pharmacological perspectives.

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Body tissues are traditionally classified as estrogen targets based on both the response to the hormone and the presence of estrogen receptors (ERs). We undertook the study on expression of ERalpha and ERbeta in the penis to identify compartments/cells responsive to estrogen, using immunohistochemistry, Western blotting, in situ hybridization, and RT-PCR analyses. Expressions of ERalpha and ERbeta in the rat penis were age dependent at both mRNA and protein levels, with the most intense signals being observed during the perinatal period and declining thereafter with age. Initial signals (fetal d 17) of ERalpha were localized to the mesenchyme and subepithelial stroma and later (postnatal d 2) to the corpus spongiosus, corpus cavernosus, and urethral epithelia. ERbeta was initially detected by postnatal d 2 and was localized diffusely in corpus spongiosus and cavernosus in immature rats. In the adult, both ERs were concentrated largely to the urethral epithelia and vascular and neuronal structures. The present study provides the first evidence for ER expression in the penis. Thus, our data add the penis to the list of estrogen-responsive tissues in males and provide a base and insight for future studies aimed at investigating a functional role of estrogen in the penis, especially in development.

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