Effects of captopril on cardiovascular reflexes and respiratory mechanisms in rats submitted to monocrotaline-induced pulmonary arterial hypertension

Wittmer, Verônica Lourenço; Waichert, Élio Junior; Gava, Pablo Lúcio; Pereira, Fausto Edmundo Lima; Guimarães, Marco César Cunegundes; Figueiredo, Suely G.; Mauad, Helder

doi:10.1016/j.pupt.2014.11.001

Cited by 7 publications

(8 citation statements)

References 36 publications

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“…Hypoxia is known to induce vasoconstriction in the pulmonary artery and to increase PAP (Yu, Glick, Schreiner, & Murphy, 1963). Wittmer et al (2015) demonstrated that MCT increases the sensitivity of peripheral chemoreceptors that sense hypoxia. They also reported that the sensitization of peripheral chemoreceptors in MCT induced PAH rats induces hyperventilation and sympathetic activation (Wittmer et al, 2015).…”

Section: Limitationsmentioning

confidence: 99%

“…Wittmer et al (2015) demonstrated that MCT increases the sensitivity of peripheral chemoreceptors that sense hypoxia. They also reported that the sensitization of peripheral chemoreceptors in MCT induced PAH rats induces hyperventilation and sympathetic activation (Wittmer et al, 2015). Given that MCT-treated rats manifest hypoxaemia and hyperventilation in a conscious state (Lingeshwar et al, 2016), the chemoreflex-activated sympathoexcitation might shift the baroreflex neural arc further to the right and the peripheral arc downwards.…”

Section: Limitationsmentioning

confidence: 99%

“…Various studies have already demonstrated baroreflex dysfunction in patients and animals with PAH by assessing baroreflex sensitivity or baroreflex-controlled SNA (Wensel et al, 2009;Wittmer et al, 2015). Changes of arterial pressure (AP) are tightly monitored by the arterial baroreceptors, and the signals from the arterial baroreceptors to brain widely and dynamically alter SNA.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, assessment of the baroreflex is essential in understanding the role of the sympathetic nervous system in PAH. Various studies have already demonstrated baroreflex dysfunction in patients and animals with PAH by assessing baroreflex sensitivity or baroreflex-controlled SNA (Wensel et al, 2009;Wittmer et al, 2015). However, these studies did not provide an assessment of the baroreflex control of AP because they evaluated baroreflex function by analysing the relationship between AP and heart rate (HR) or SNA under the baroreflex closed-loop condition.…”

Section: Introductionmentioning

confidence: 99%

“…Wensel et al (2009) reported baroreflex dysfunction in PAH patients using the slope of the linear correlation between the R-R interval and systolic blood pressure Wittmer et al (2015). reported that MCT blunts the changes in AP and HR after administration of phenylephrine and nitroprusside, indicating worsening of baroreflex sensitivity.…”

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confidence: 99%

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Suppressed baroreflex peripheral arc overwhelms augmented neural arc and incapacitates baroreflex function in rats with pulmonary arterial hypertension

Shinoda

Saku

Oga

et al. 2019

Experimental Physiology

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New Findings What is the central question of this study?The impact of pulmonary arterial hypertension on open‐loop baroreflex function, which determines how powerfully and rapidly the baroreflex operates to regulate arterial pressure, remains poorly understood. What is the main finding and its importance?The gain of the baroreflex total arc, indicating the baroreflex pressure‐stabilizing function, is markedly attenuated in rats with monocrotaline‐induced pulmonary arterial hypertension. This is caused by a rightward shift of the baroreflex neural arc and a downward shift of the peripheral arc. These findings contribute greatly to our understanding of arterial pressure regulation by the sympathetic nervous system in pulmonary arterial hypertension. Abstract Sympathoexcitation has been documented in patients with established pulmonary arterial hypertension (PAH). Although the arterial baroreflex is the main negative feedback regulator of sympathetic nerve activity (SNA), the way in which PAH impacts baroreflex function remains poorly understood. In this study, we conducted baroreflex open‐loop analysis in a rat model of PAH. Sprague–Dawley rats were injected with monocrotaline (MCT) s.c. to induce PAH (60 mg kg−1; n = 11) or saline as a control group (CTL; n = 8). At 3.5 weeks after MCT injection, bilateral carotid sinuses were isolated, and intrasinus pressure (CSP) was controlled while SNA at the coeliac ganglia and arterial pressure (AP) were recorded. To examine the static baroreflex function, CSP was increased stepwise while steady‐state AP (total arc) and SNA (neural arc) responses to CSP and the AP response to SNA (peripheral arc) were measured. Monocrotaline significantly decreased the static gain of the baroreflex total arc at the operating AP compared with CTL (−0.80 ± 0.31 versus −0.22 ± 0.22, P < 0.05). Given that MCT markedly increased plasma noradrenaline, an index of SNA, by approximately 3.6‐fold compared with CTL, calibrating SNA by plasma noradrenaline revealed that MCT shifted the neural arc to a higher SNA level and shifted the peripheral arc downwards. Monocrotaline also decreased the dynamic gain of the baroreflex total arc (−0.79 ± 0.16 versus −0.35 ± 0.17, P < 0.05), while the corner frequencies that reflect the speed of the baroreflex remained unchanged (0.06 ± 0.02 versus 0.08 ± 0.02 Hz, n.s.). In rats with MCT‐induced PAH, the suppressed baroreflex peripheral arc overwhelms the augmented neural arc and, in turn, attenuates the gain of the total arc, which determines the pressure‐stabilizing capacity of the baroreflex.

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Section: Limitationsmentioning

confidence: 99%

Section: Limitationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Suppressed baroreflex peripheral arc overwhelms augmented neural arc and incapacitates baroreflex function in rats with pulmonary arterial hypertension

Shinoda

Saku

Oga

et al. 2019

Experimental Physiology

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Captopril improves postresuscitation hemodynamics protective against pulmonary embolism by activating the ACE2/Ang-(1-7)/Mas axis

Xiao

Liu

Zhao

et al. 2016

Naunyn-Schmiedeberg's Arch Pharmacol

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Acute pulmonary embolism (APE) has a very high mortality rate, especially at cardiac arrest and even after the return of spontaneous circulation (ROSC). This study investigated the protective effect of the angiotensin-converting enzyme (ACE) inhibitor captopril on postresuscitation hemodynamics, in a porcine model of cardiac arrest established by APE. Twenty-nine Beijing Landrace pigs were infused with an autologous thrombus leading to cardiac arrest and subjected to standard cardiopulmonary resuscitation and thrombolysis. Ten resuscitated pigs were randomly and equally apportioned to receive either captopril (22.22 mg/kg) infusion or the same volume saline, 30 min after ROSC. Hemodynamic changes and ACE-Ang II-angiotensin II type 1 receptor (AT1R) and ACE2/Ang-(1-7)/Mas receptor axis levels were determined. APE was associated with a decline in mean arterial pressure and a dramatic increase in pulmonary artery pressure and mean right ventricular pressure. After ROSC, captopril infusion was associated with significantly lower mean right ventricular pressure and systemic and pulmonary vascular resistance, faster heart rate, and higher Ang-(1-7) levels, ACE2/ACE, and Ang-(1-7)/Ang II, compared with the saline infusion. The ACE2/Ang-(1-7)/Mas pathway correlated negatively with external vascular lung water and pulmonary vascular permeability and positively with the right cardiac index. In conclusion, in a pig model of APE leading to cardiac arrest, captopril infusion was associated with less mean right ventricular pressure overload after resuscitation, compared with saline infusion. The reduction in systemic and pulmonary vascular resistance associated with captopril may be by inhibiting the ACE-Ang II-AT1R axis and activating the ACE2/Ang-(1-7)/Mas axis.

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Angiotensin-converting enzyme inhibitors, angiotensin II receptors antagonists, beta-blockers and ivabradine as supportive therapy in pulmonary hypertension: Drug safety and tolerability

Correale

Zicchino

Monaco

et al. 2017

European Journal of Internal Medicine

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Effects of captopril on cardiovascular reflexes and respiratory mechanisms in rats submitted to monocrotaline-induced pulmonary arterial hypertension

Cited by 7 publications

References 36 publications

Suppressed baroreflex peripheral arc overwhelms augmented neural arc and incapacitates baroreflex function in rats with pulmonary arterial hypertension

Suppressed baroreflex peripheral arc overwhelms augmented neural arc and incapacitates baroreflex function in rats with pulmonary arterial hypertension

Captopril improves postresuscitation hemodynamics protective against pulmonary embolism by activating the ACE2/Ang-(1-7)/Mas axis

Angiotensin-converting enzyme inhibitors, angiotensin II receptors antagonists, beta-blockers and ivabradine as supportive therapy in pulmonary hypertension: Drug safety and tolerability

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