Introduction Earlier studies have shown that sildenafil may modify some aspects of male rat sexual behavior and sexual incentive motivation. Stimulation of endothelial nitric oxide synthase (eNOS) has also been reported to affect sexual motivation in old rats. Aim To determine the effects of sildenafil and a compound stimulating eNOS on copulatory behavior and sexual incentive motivation in young adult Fisher 344 and Wistar male rats. Methods The rats were selected for a low intromission ratio, and then treated with Impaza (stimulator of eNOS), sildenafil, or Impaza + sildenafil for 28 days. Tests for copulatory behavior and sexual incentive motivation were performed before the beginning of treatment and at days 7, 14, and 28 of treatment. Main Outcome Measures Standard parameters of copulatory behavior and sexual incentive motivation. Measurements of penis length at mount, intromission, and ejaculation. Results The Fisher 344 rats displayed a higher level of sexual incentive motivation than the Wistar rats, while the copulatory behavior was similar in both strains. Impaza and sildenafil enhanced the sexual incentive motivation after 28 days of treatment in the Wistar rats, but failed to do so in the Fisher 344 rats. The copulatory behavior was unaffected in the Wistar strain, while the Fisher 344 males had an enhanced intromission ratio after treatment with Impaza and sildenafil for 28 days. Conclusions The nitric oxide-guanylyl cyclase pathway seems to be of importance for sexual incentive motivation in animals with a modest baseline level. The different drug effects in the Wistar and Fisher 344 rats can be attributed to baseline differences. The importance of eNOS for sexual functions should not be overlooked.
Experimental NO deficiency induced by L-NAME injection led to the development of arterial hypertension, endothelial dysfunction, and cardiomyocyte hypertrophy and reduced blood content of nitrates and nitrites. Impaza, NO donors, activators of NO-synthase, antioxidants, and antihypertensive preparations produced endothelium-protective effect of different degree.
Endothelial nitric oxide synthase (eNOS) has an important role in erection, and it also affects aspects of sexual behavior. In this experiment, we determined whether a compound enhancing the activity of eNOS, Impaza, could stimulate any aspect of sexual behavior and increase penis length in rats with a high baseline of sexual activity. For comparison, the PDE5 inhibitor sildenafil was included. Male rats were orally treated with Impaza or sildenafil for 28 days. Impaza (3 ml kg(-1)) was given daily while sildenafil (3 mg kg(-1)) was given twice weekly. Tests for sexual incentive motivation and copulatory behavior were performed just before drug treatment and at days 7, 14 and 28 of treatment. In addition, the length of the protruding penis at mount, intromission and ejaculation was measured. Impaza but not sildenafil increased penis length at mount after 14 and 28 days of treatment. The compounds failed to modify sexual incentive motivation or copulatory behavior. It is suggested that Impaza enhanced intracavernous pressure, as such a pressure increase is the most likely explanation for enhanced penis length at mount. This effect, together with an absence of motivational actions, suggests that Impaza may be the most valuable treatment for erectile dysfunction.
Modeling of NO deficiency by administration of L-NAME to rats led to the development of arterial hypertension and endothelial dysfunction. Pronounced endothelium and cardioprotective effects of impaza under these experimental conditions manifested more markedly during combined administration of the preparation with standard hypotensive preparations enalapril and losartan.
The effectiveness of antibody-based release-active preparations Impaza (antibodies to eNOS), Tenoten (antibodies to brain-specific protein S-100), Dietressa (antibodies to type 1 cannabinoid receptor), Brizantin (combined preparation, antibodies to brain-specific protein S-100 and type 1 cannabinoid receptor), and Divaza (combined preparation, antibodies to brain-specific protein S-100 and eNOS) in the prevention of vertigo was studied on the model of intermittent accumulation of Coriolis accelerations (ICCA). Modification of activity of vestibular receptors and signal systems by release-active preparations contributed to an increase in ICCA tolerance time. Combined preparation Impaza possessed the most significant antinaupathic properties. Brizantin was less potent in this respect.
Болезнь Альцгеймера (БА) является одним из наибо-лее социально значимых заболеваний, которому, как пра-вило, подвержены лица старшей возрастной группы. При БА отмечается комплексное нарушение структуры и функции мозга: дисфункция базальной холинергической системы, нарушение синаптической пластичности, уменьшение численности нейронов. Дисфункция базаль-ной холинергической системы заключается в том, что в аксонах холинергических нейронов, оказавшихся в зоне *e-mail: tanaevakk@materiamedica.ru накопления растворимых олигомеров бета-амилоида (но-вая кора, гиппокамп, миндалина), развивается затухаю-щая ретроградная нейропатия [1]. Она проявляется нару-шением ремоделирования терминалей аксонов, ослабле-нием синтеза, транспорта и усилением обратного захвата ацетилхолина в нейронах базальной холинергической си-стемы. Нарушение синаптической пластичности в ука-занных зонах приводит к ослаблению долговременной потенциации синаптического проведения и усилению его Цель исследования. Проверка предположения, что препарат диваза, состоящий из релиз-активных антител (РА АТ) к белку S100 и NO-синтетазе (eNOS), может обладать антиамнестическим действием. Материал и методы. Исследование проводили на модели амнезии, вызванной интрацеребровентрикулярной инъекцией фрагмента β-амилоидного пептида 25-35 крысам. Оценивали способность РА АТ к белку S100 (тенотен) и eNOS (импаза) их комбинации -дивазы компенсировать поведенческие отклонения в тестах распознавания новых объектов и условной реакции пассивного избегания. Результаты. Под влиянием РА АТ к S100 наблюдалось восстановление нарушенной кратковременной памяти, РА АТ к eNOS были более эффективны в более позднем периоде (через 24 часа). Комбинированный препарат полностью компенсировал смоделированные нарушения. Кроме того, если тенотен оказывал максимальное влияние на когнитивные функции, то импаза больше действовала на эмоциональную составляющую. Диваза оказывала более эффективное влияние на амнезию, при этом сочетая свойства обоих компонентов и взаимно усиливая их. Заключение. Полученные данные подтверждают перспективность дальнейшего исследования релиз-активных препаратов при нейродегенеративных нарушениях.Ключевые слова: амнезия, болезнь Альцгеймера, диваза, импаза, тенотен. Objective. On amnesia models induced by (icv) injection of β-amyloid fragment 25-35 peptide were evaluated antiamnestic actitity. Material and methods. It was used of active antibody preparations (RA AT) to protein S100 (tenoten), to eNOS (impaza) and combinations (divaza) antiamnestic activity behavioral tests novel object conditioned response passive avoidance. Results. Under the influence of RA AT S100 observed recovery of violation of the β-amyloid short-term memory (1 hour after the initial presentation of objects), and RA AT eNOS were more effective when tested 24 hours later. Combined medication completely compensate for the simulated deflection behavior of rats did not differ from the intact control. The CRPA RA AT S100 had the greatest impact on the LP entry into the dark compartment, and RA AT eNOS i...
Experiment on ISIAH rats showed that antibodies to endothelial NO synthase in ultralow doses (impaza) produced a mild and progressive antihypertensive effect slightly inferior to that of losartan. The use of impaza is perspective in patients with erectile dysfunction and cardiovascular pathology.
Release-active antibodies to S100 protein enhanced the latency period of the disease, reduced its peak intensity and compensated the loss of body weight of the animals. The experimental drug effect was similar to the results of copaxone injections.
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