Effects of nitric oxide synthesis inhibitor or fluoxetine treatment on depression-like state and cardiovascular changes induced by chronic variable stress in rats

Comorbidity between mood disorders and cardiovascular disease has been described extensively. However, available antidepressants can have cardiovascular side effects. Treatment with selective inhibitors of neuronal nitric oxide synthase (nNOS) induces antidepressant effects, but whether the antidepressant-like effects of these drugs are followed by cardiovascular changes has not been previously investigated. Here, we tested in male rats exposed to chronic variable stress (CVS) the hypothesis that nNOS blockers are advantageous compared with conventional antidepressants in terms of cardiovascular side effects. We compared the effects of chronic treatment with the preferential nNOS inhibitor 7-nitroindazole (7-NI) with those evoked by the conventional antidepressant fluoxetine on alterations that are considered as markers of depression (immobility in the forced swimming test, FST, decreased body weight gain and increased plasma corticosterone concentration) and cardiovascular changes caused by CVS. Rats were exposed to a 14-day CVS protocol, while being concurrently treated daily with either 7-NI (30 mg/kg) or fluoxetine (10 mg/kg). Fluoxetine and 7-NI prevented the increase in immobility in the FST induced by CVS and reduced plasma corticosterone concentration in stressed rats. Both these treatments also prevented the CVS-evoked reduction of the depressor response to vasodilator agents and baroreflex changes. Fluoxetine and 7-NI-induced cardiovascular changes independent of stress exposure, including cardiac autonomic imbalance, increased intrinsic heart rate and vascular sympathetic modulation, a reduction of the pressor response to vasoconstrictor agents, and impairment of baroreflex activity. Altogether, these findings provide evidence that fluoxetine and 7-NI have similar effects on the depression-like state induced by CVS and on cardiovascular function.

Adolescent vulnerability to cardiovascular consequences of chronic social stress: Immediate and long-term effects of social isolation during adolescence

It has been demonstrated that disruption of social bonds and perceived isolation (loneliness) are associated with an increased risk of cardiovascular morbidity and mortality. Adolescence is proposed as a period of vulnerability to stress. Nevertheless, the impact of chronic social stress during this ontogenic period in cardiovascular function is poorly understood. Therefore, the purpose of this study was to compare the impact in cardiovascular function of social isolation for 3 weeks in adolescent and adult male rats. Also, the long-term effects of social isolation during adolescence were investigated longitudinally. Social isolation reduced body weight in adolescent, but not in adult animals. Disruption of social bonds during adolescence increased arterial pressure without affecting heart rate and pulse pressure (PP). Nevertheless, social isolation in adulthood reduced systolic arterial pressure and increased diastolic arterial pressure, which in turn decreased PP without affecting mean arterial pressure. Cardiovascular changes in adolescents, but not adults, were followed by facilitation of both baroreflex sensitivity and vascular reactivity to the vasodilator agent acetylcholine. Vascular responsiveness to either the vasodilator agent sodium nitroprusside or the vasoconstrictor agent phenylephrine was not affected by social isolation. Except for the changes in body weight and baroreflex sensitivity, all alterations evoked by social isolation during adolescence were reversed in adulthood after moving animals from isolated to collective housing. These findings suggest a vulnerability of adolescents to the effects of chronic social isolation in cardiovascular function. However, results indicate minimal cardiovascular consequences in adulthood of disruption of social bonds during adolescence. © 2015 Wiley Periodicals, Inc. Develop Neurobiol, 2015.

Efeitos do halotano, isoflurano e sevoflurano nas respostas cardiovasculares ao pinçamento aórtico infra-renal: estudo experimental em cães

JUSTIFICATIVA E OBJETIVOS: O pinçamento infra-renal da aorta abdominal pode produzir alterações hemodinâmicas. O objetivo do estudo foi avaliar os efeitos do halotano, isoflurano e sevoflurano sobre a função cardiovascular, em cães submetidos à pinçamento aórtico infra-renal. MÉTODO: O estudo aleatório foi realizado em 30 cães, distribuídos em três grupos, de acordo com o anestésico halogenado utilizado durante a anestesia, em concentrações equipotentes de 0,75 CAM: GH (n=10) - halotano a 0,67%; GI (n=10) - isoflurano a 0,96%; e GS (n=10) - sevoflurano a 1,8%. em todos os animais foi realizada ligadura infra-renal da aorta, por período de 30 min. Os atributos hemodinâmicos foram estudados nos momentos: C (Controle), Ao15 e Ao30, respectivamente após 15 e 30 minutos do pinçamento aórtico, e DAo e DAo15, respectivamente, imediatamente e após 15 min do despinçamento aórtico. RESULTADOS: Durante o pinçamento aórtico houve, em todos os grupos, aumento das pressões arterial média e do átrio direito, e dos índices cardíaco, sistólico e de trabalho sistólico dos ventrículos direito e esquerdo. A pressão da artéria pulmonar aumentou em GI e GS e a pressão pulmonar ocluída em GH e GI. Após o despinçamento aórtico, houve normalização dos atributos que haviam se elevado, com exceção dos índices cardíaco e sistólico, que continuaram elevados, acompanhados de diminuição do índice de resistência vascular sistêmica. Não houve diferença significante entre os grupos em relação aos atributos estudados, com exceção da freqüência cardíaca que foi sempre menor em GH, em relação aos demais grupos, durante o pinçamento e despinçamento aórtico. CONCLUSÕES: No cão, nas condições experimentais empregadas, a inalação do halotano, isoflurano e sevoflurano em concentrações equipotentes (0,75 CAM) não atenua as respostas cardiovasculares ao pinçamento aórtico infra-renal.

Efeitos da clonidina nas respostas cardiovasculares ao pinçamento aórtico infra-renal: estudo experimental no cão

JUSTIFICATIVA E OBJETIVOS: O pinçamento aórtico infra-renal pode determinar alterações cardiovasculares. A clonidina, um alfa2-agonista, determina bradicardia e diminuição da pressão arterial. O objetivo do estudo foi avaliar os efeitos da clonidina sobre a função cardiovascular, em cães submetidos a pinçamento aórtico infra-renal. MÉTODO: O estudo aleatório foi realizado em 16 cães, distribuídos em dois grupos: G Controle - sem a utilização de clonidina e G Clon - clonidina, na dose inicial de 5 µg.kg-1, por via venosa, imediatamente antes do pinçamento aórtico infra-renal, seguido de 2 µg.min-1.m² até o final do estudo. em todos os animais foi realizada ligadura infra-renal da aorta, por 45 minutos. Os atributos hemodinâmicos foram estudados nos momentos C (controle), após 10 (Ao10) e 25 (Ao25) minutos do pinçamento aórtico, e após 10 (DAo10) e 25 (DAo25) minutos do despinçamento aórtico. RESULTADOS: Durante o pinçamento aórtico, houve diferença significante entre os grupos, em relação à freqüência cardíaca, pressão arterial média e índice cardíaco (G Controle > G Clon). Após o despinçamento aórtico houve diferença significante entre os grupos, em relação à freqüência cardíaca (G Controle > G Clon) e pressões do átrio direito e da artéria pulmonar ocluída (G Clon > G Controle). Durante o pinçamento aórtico, houve nos dois grupos, aumento significante das pressões de átrio direito e artéria pulmonar ocluída, dos índices sistólico e do trabalho sistólico do ventrículo esquerdo, e diminuição do índice de resistência vascular pulmonar. No grupo controle houve aumento significante das pressões arterial média e da artéria pulmonar, e dos índices cardíaco e do trabalho sistólico do ventrículo direito. No grupo clonidina, houve diminuição significante da freqüência cardíaca. Após o despinçamento aórtico, houve nos dois grupos: diminuição significante da freqüência cardíaca e pressão arterial média, enquanto os valores das pressões do átrio direito e índice sistólico continuaram elevados. No grupo controle, os valores do índice de trabalho sistólico do ventrículo direito continuaram elevados enquanto os valores do índice cardíaco retornaram a valores próximos aos do controle. No grupo clonidina, os valores das pressões do átrio direito e da artéria pulmonar ocluída, e o índice sistólico, continuaram significantemente elevados. CONCLUSÕES: No cão, nas condições experimentais empregadas, a administração venosa contínua de clonidina atenua as respostas cardiovasculares decorrentes do pinçamento aórtico infra-renal.

Endogenous hydrogen peroxide in the hypothalamic paraventricular nucleus regulates sympathetic nerve activity responses to L-glutamate

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

O óxido nítrico (NO) no controle neural da pressão arterial: Modulação da transmissão glutamatérgica no NTS

The neuromodulatory effect of nitric oxide (NO) on glutamatergic transmission within the NTS related to cardiovascular regulation has been widely investigated. Activation of glutamatergic receptors in the NTS stimulates the production and release of NO and other nitrosyl substances with neurotransmitter/neuromodulator properties. The presence of NOS, including the protein nNOS and its mRNA in vagal afferent terminals in the NTS and nodose ganglion cells suggest that NO can act on glutamatergic transmission. We previously reported that iontophoresis of L-NAME on NTS neurons receiving vagal afferent inputs significantly decreased the number of action potentials evoked by iontophoretic application of AMPA. In addition, iontophoresis of the NO donor papaNONOate enhanced spontaneous discharge and the number of action potentials elicited by AMPA, suggesting that NO could be facilitating AMPA-mediated neuronal transmission within the NTS. Furthermore, the changes in renal sympathetic discharge during activation of baroreceptors and cardiopulmonary receptors involve activation of AMPA and NMDA receptors in the NTS and these responses are attenuated by microinjection of L-NAME in the NTS of conscious and anesthetized rats. Cardiovascular responses elicited by application of NO in the NTS are closely similar to those obtained after activation of vagal afferent inputs, and L-glutamate is the main neurotransmitter of vagal afferent fibers. In this review we discuss the possible neuromodulatory mechanisms of central produced/released NO on glutamatergic transmission within the NTS.

Espécies reativas de oxigênio no controle neurovegetativo da pressão arterial

The control of the blood pressure depends on the activity of select groups of neurons present in the central nervous system. Evidence has demonstrated that the redox state (a balance between oxidizing and reducing species) is involved in the control of neuronal activity, which suggests that the redox state can influence the neuronal transmission within the central nervous system acting on the neuronal modulation of biological functions. For instance, the glutamatergic transmission may be widely affected by reactive oxygen species, oxidizing agents that have been extensively investigated due to their involvement in physiological and pathological processes. In the present article, we discuss the main experimental finds that support the hypothesis that reactive oxygen species have important role in physiological (and pathological) modulation of the cardiovascular function through alterations in the sympathetic and parasympathetic system. Therefore, reactive oxygen species can actively participate in the development of cardiovascular diseases like hypertension when the balance in the redox state is disrupted.

Mechanisms in the bed nucleus of the stria terminalis involved in control of autonomic and neuroendocrine functions: A review

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Avaliação da função cardíaca em cães com anemia normovolência aguda experimental

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Influência do treinamento físico intervalado nas pressões respiratórias na concentração de nitrito/nitrato e do receptor de leptina solúvel em mulheres na pós-menopausa

Pós-graduação em Ciências da Motricidade - IBRC

Involvement of the median preoptic nucleus in blood pressure control

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Stress vulnerability during adolescence

Objective: This study investigated the physiological and somatic changes evoked by daily exposure to the same type of stressor (homotypic) or different aversive stressor stimuli (heterotypic) in adolescent and adult rats, with a focus on cardiovascular function. The long-term effects of stress exposure during adolescence were also investigated longitudinally. Methods: Male Wistar rats were exposed to repeated restraint stress (RRS, homotypic) or chronic variable stress (CVS, heterotypic). Results: Adrenal hypertrophy, thymus involution, and elevated plasma glucocorticoid were observed only in adolescent animals, whereas reduction in body weight was caused by both stress regimens in adults. CVS increased mean arterial pressure (adolescent: p = .001; adult: p = .005) and heart rate (HR; adolescent: p = .020; adult: p = .011) regardless of the age, whereas RRS increased blood pressure selectively in adults (p = .001). Rest tachycardia evoked by CVS was associated with increased cardiac sympathetic activity in adults, whereas a decreased cardiac parasympathetic activity was observed in adolescent animals. Changes in cardiovascular function and cardiac autonomic activity evoked by both CVS and RRS were followed by alterations in baroreflex activity and vascular reactivity to vasoconstrictor and vasodilator agents in adolescent adult animals. Except for the circulating glucocorticoid change, all alterations observed during adolescence were reversed in adulthood. Conclusions: These findings suggest a stress vulnerability of adolescents to somatic and neuroendocrine effects regardless of stress regimen. Our results indicated an age-stress type-specific influence in stress-evoked cardiovascular/autonomic changes. Data suggest minimal consequences in adulthood of stress during adolescence.

Stress vulnerability during adolescence: comparison of chronic stressors in adolescent and adult rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)