Role of hydrogen sulfide in ventilatory responses to hypercapnia in the medullary raphe of adult rats.

NEW FINDINGS: What is the central question of this study? There is evidence that H2 S plays a role in the control of breathing: what are its actions on the ventilatory and thermoregulatory responses to hypercapnia via effects in the medullary raphe, a brainstem region that participates in the ventilatory adjustments to hypercapnia? What is the main finding and its importance? Hypercapnia increased the endogenous production of H2 S in the medullary raphe. Inhibition of endogenous H2 S attenuated the ventilatory response to hypercapnia in unanaesthetized rats, suggesting its excitatory action via the cystathionine ß-synthase-H2 S pathway in the medullary raphe. ABSTRACT: Hydrogen sulfide (H2 S) has been recently recognized as a gasotransmitter alongside carbon monoxide (CO) and nitric oxide (NO). H2 S seems to modulate the ventilatory and thermoregulatory responses to hypoxia and hypercapnia. However, the action of the H2 S in the medullary raphe (MR) on the ventilatory responses to hypercapnia remains to be elucidated. The present study aimed to assess the role of H2 S in the MR (a brainstem region that contains CO2 -sensitive cells and participates in the ventilatory adjustments to hypercapnia) in the ventilatory responses to hypercapnia in adult unanaesthetized Wistar rats. To do so, aminooxyacetic acid (AOA; a cystathionine ß-synthase (CBS) enzyme inhibitor), propargylglycine (PAG; a cystathionine γ-lyase enzyme inhibitor) and sodium sulfide (Na2 S; an H2 S donor) were microinjected into the MR. Respiratory frequency (fR ), tidal volume (VT ), ventilation ( V̇E ), oxygen consumption ( V̇O2 ) and body temperature (Tb ) were measured under normocapnic (room air) and hypercapnic (7% CO2 ) conditions. H2 S concentration within the MR was determined. Microinjection of the drugs did not affect fR , VT and V̇E during normocapnia when compared to the control group. However, the microinjection of AOA, but not PAG, attenuated fR and V̇E during hypercapnia in comparison to the vehicle group, but had no effects on Tb . In addition, we observed an increase in the endogenous production of H2 S in the MR during hypercapnia. Our findings indicate that endogenously produced H2 S in the MR plays an excitatory role in the ventilatory response to hypercapnia, acting through the CBS-H2 S pathway.

Cigarette smoke exposure causes systemic and autonomic cardiocirculatory changes in rats depending on the daily exposure dose.

AIMS: To evaluate the systemic changes and autonomic cardiocirculatory control of awaken rats chronically exposed to the cigarette smoke (CS) of 1 or 2 cigarettes/day. MAIN METHODS: Rats were exposed to clean air (control) or cigarette smoke of 1 (CS1) or 2 (CS2) cigarettes/animal/day for 30 days. Then, arterial pressure (AP) and heart rate (HR) were recorded in conscious rats to assess spontaneous baroreflex sensitivity and HR and AP variabilities. Evoked baroreflex and cardiac autonomic tone were evaluated by vasoactive drugs and autonomic blockers, respectively. In another group, ventilatory and cardiovascular parameters were recorded under hypoxia and hypercapnia stimulus. At the end of protocols, heart, lung, kidneys and liver were collected for histological analysis. KEY FINDINGS: Rats exposed to CS showed morphological changes, being more evident in the CS2 group. Also, less weight gain and cardiac hypertrophy were prominent in CS2 rats. Basal AP and HR, spontaneous baroreflex sensitivity and cardiovascular variabilities were similar among groups. CS exposure progressively blunted the bradycardia response to phenylephrine (-2.2 ± 0.1 vs. -1.7 ± 0.2 vs. -1.5 ± 0.2) while the tachycardia response to sodium nitroprusside was slightly increased compared to control. Vagal tone was not affected by CS, but CS2 rats exhibited higher sympathetic tone (-25 ± 4 vs. -28 ± 4 vs. -56 ± 9) and lower intrinsic HR (411 ± 4 vs. 420 ± 8 vs. 390 ± 6). Exposure to CS of 2 cigarettes also exacerbated the reflex cardiovascular and ventilatory responses to hypoxia and hypercapnia. SIGNIFICANCE: CS exposure for 30 days promoted systemic changes and autonomic cardiocirculatory dysfunction in rats depending on the daily exposure dose.

Benefits of pharmacological and electrical cholinergic stimulation in hypertension and heart failure.

Systemic arterial hypertension and heart failure are cardiovascular diseases that affect millions of individuals worldwide. They are characterized by a change in the autonomic nervous system balance, highlighted by an increase in sympathetic activity associated with a decrease in parasympathetic activity. Most therapeutic approaches seek to treat these diseases by medications that attenuate sympathetic activity. However, there is a growing number of studies demonstrating that the improvement of parasympathetic function, by means of pharmacological or electrical stimulation, can be an effective tool for the treatment of these cardiovascular diseases. Therefore, this review aims to describe the advances reported by experimental and clinical studies that addressed the potential of cholinergic stimulation to prevent autonomic and cardiovascular imbalance in hypertension and heart failure. Overall, the published data reviewed demonstrate that the use of central or peripheral acetylcholinesterase inhibitors is efficient to improve the autonomic imbalance and hemodynamic changes observed in heart failure and hypertension. Of note, the baroreflex and the vagus nerve activation have been shown to be safe and effective approaches to be used as an alternative treatment for these cardiovascular diseases. In conclusion, pharmacological and electrical stimulation of the parasympathetic nervous system has the potential to be used as a therapeutic tool for the treatment of hypertension and heart failure, deserving to be more explored in the clinical setting.

Avaliação da dissociação iônica do hidróxido de cálcio associado ao Aloe vera como veículo / Evaluation of ionic dissociation of calcium hydroxide associated with Aloe vera as vehicle

Introdução : O hidróxido de cálcio é considerado uma medicação intracanal padrão ouro e diferentes substâncias podem ser empregadas como veículo para melhorar suas propriedades. O Aloe vera é um fitoterápico popularmente conhecido por babosa e que se destaca pela sua capacidade imunorreguladora, antimicrobiana, cicatrizante e pela biocompatibilidade celular. Objetivo: Avaliar a dissociação iônica do hidróxido de cálcio, tendo o Aloe vera como veículo. Material e método: O extrato de Aloe vera foi obtido diretamente da folha, submetido à filtração e armazenado em tubo Falcon estéril. Foram preparados dois grupos de medicação intracanal: o grupo controle, com hidróxido de cálcio e soro fisiológico, e o grupo experimental, com hidróxido de cálcio e Aloe vera como veículo. Resultado: Não foi verificada uma diferença estatisticamente significativa entre as médias de liberação de cálcio dos grupos (p=0,944). Quando comparados os valores de forma pareada, considerando as diferentes avaliações ao longo do tempo, foi identificada uma diferença estatisticamente significativa (p=0,015) para o grupo experimental, de modo que os valores médios da liberação de cálcio foram superiores até o 21º dia do estudo. Conclusão: O hidróxido de cálcio, quando associado ao Aloe vera, apresentou maior dissociação iônica que quando utilizado com água destilada. Tal resultado, associado às propriedades inerentes deste fitoterápico, sugerem que a pasta de hidróxido de cálcio e Aloe vera pode ser uma alternativa viável e promissora como medicação intracanal, e melhorar o reparo apical e periapical.

Introduction: Calcium hydroxide is considered an intracanal medication gold standard, and different substances can be employed as a vehicle to improve its properties. Aloe vera is a herbal remedy popularly known as babosa and is notable for its immunoregulatory, antimicrobial, healing and cellular biocompatibility. Objective: To evaluate the ionic dissociation of calcium hydroxide, with the Aloe vera as vehicle. Material and method: The extract of Aloe vera was obtained directly from the leaf, submitted to filtration and stored in a sterile falcon tube. Two groups of intracanal medication were prepared; the control group, with calcium hydroxide and saline; and the experimental group, with calcium hydroxide and Aloe vera as vehicle. Result: There was no statistically significant difference between the means of calcium release from the groups (p = 0.944). When comparing the paired values, considering the different evaluations over time, a statistically significant difference (p = 0.015) was identified for the experimental group, so that mean values of calcium released were higher up to the 21st day of the study. Conclusion: Calcium hydroxide, when associated with Aloe vera, presented higher ionic dissociation than when used with distilled water. This result, combined with the inherent properties of this herbal remedy, suggests that the paste of calcium hydroxide and Aloe vera can be a viable and promising alternative as intracanal medication and improve apical and periapical repair.