Sex Hormones Promote Opposite Effects on ACE and ACE2 Activity, Hypertrophy and Cardiac Contractility in Spontaneously Hypertensive Rats.

BACKGROUND: There is growing interest in sex differences and RAS components. However, whether gender influences cardiac angiotensin I-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) activity is still unknown. In the present work, we determined the relationship between ACE and ACE2 activity, left ventricular function and gender in spontaneously hypertensive rats (SHRs). METHODOLOGY/PRINCIPAL FINDINGS: Twelve-week-old female (F) and male (M) SHRs were divided into 2 experimental groups (n = 7 in each group): sham (S) and gonadectomized (G). Fifty days after gonadectomy, we measured positive and negative first derivatives (dP/dt maximum left ventricle (LV) and dP/dt minimum LV, respectively), hypertrophy (morphometric analysis) and ACE and ACE2 catalytic activity (fluorimetrically). Expression of calcium handling proteins was measured by western blot. Male rats exhibited higher cardiac ACE and ACE2 activity as well as hypertrophy compared to female rats. Orchiectomy decreased the activity of these enzymes and hypertrophy, while ovariectomy increased hypertrophy and ACE2, but did not change ACE activity. For cardiac function, the male sham group had a lower +dP/dt than the female sham group. After gonadectomy, the +dP/dt increased in males and reduced in females. The male sham group had a lower -dP/dt than the female group. After gonadectomy, the -dP/dt increased in the male and decreased in the female groups when compared to the sham group. No difference was observed among the groups in SERCA2a protein expression. Gonadectomy increased protein expression of PLB (phospholamban) and the PLB to SERCA2a ratio in female rats, but did not change in male rats. CONCLUSION: Ovariectomy leads to increased cardiac hypertrophy, ACE2 activity, PLB expression and PLB to SERCA2a ratio, and worsening of hemodynamic variables, whereas in males the removal of testosterone has the opposite effects on RAS components.

Testosterone induces apoptosis in cardiomyocytes by increasing proapoptotic signaling involving tumor necrosis factor-α and renin angiotensin system.

Anabolic androgenic steroids lead to cardiac complications and have been shown to exhibit proapoptotic effects in cardiac cells; however, the mechanism involved in those effects is unclear. The aim of this study was to assess whether apoptosis and the activation of caspase-3 (Casp-3) induced by testosterone in high concentrations involves increments in tumor necrosis factor-α (TNF-α) concentrations and angiotensin-converting enzyme (ACE) activity in cardiomyocytes (H9c2) cell cultures. Cardiomyocytes were treated with testosterone (5 × 10(-6) mol/L), doxorubicin (9.2 × 10(-6) mol/L), testosterone + etanercept (Eta; 6.67 × 10(-5) mol/L), testosterone + losartan (Los; 10(-7) mol/L), and testosterone + AC-DEVD-CHO (10(-5) mol/L; Casp-3 inhibitor). Apoptosis was determined by flow cytometry and by the proteolytic activity of Casp-3. We demonstrated that incubation of H9c2 cells for 48 h with testosterone causes the apoptotic death of 60-70% of the cells and co-treatments with Eta, Los, or AC-DEVD-CHO reduced this effect. Testosterone also induces apoptosis (concentration dependent) and increases the proteolytic activity of Casp-3, which were reduced by co-treatments. TNF-α and ACE activities were elevated by testosterone treatment, while co-treatment with Los and Eta reduced these effects. We concluded that an interaction between testosterone, angiotensin II, and TNF-α induced apoptosis and Casp-3 activity in cultured cardiomyocytes, which contributed to the reduced viability of these cells induced by testosterone in toxic concentrations.

Atividade gastroprotetora do extrato etanólico de Pavonia alnifolia A. St. -Hil / Gastro protective activity of the Pavonia alnifolia A.St. -Hil. extract

RESUMO No Brasil, a família Malvaceae está representada por aproximadamente 200 espécies e algumas foram descritas como gastroproteroras. Pavonia alnifolia A.St.-Hil. (Malvaceae) foi selecionada após uma abordagem quimiossistemática, considerando-se sua potencial capacidade em prevenir lesões gástricas. Assim, a atividade gastroprotetora do extrato etanólico de caules de P. alnifolia foi avaliada utilizando o modelo de indução aguda da lesão gástrica por etanol acidificado em camundongos. Além disso, foram quantificados o teor de flavonóides, pelo método de cloreto de alumínio, e de polifenóis, pelo método Folin-Ciocalteu, uma vez que a relação desses componentes com a proteção gástrica foi evidenciada. Os ensaios apontaram redução acentuada das lesões gástricas em camundongos tratados com o extrato da planta em todas as doses ensaiadas (10, 100 e 300 mg/kg). Esse efeito pode estar relacionado com a presença de polifenóis, cujo teor encontrado foi 74,3 ± 7,5 µg equivalente de pirogalol/mg do material vegetal examinado e 82,7 ± 7,1 µg equivalente de pirogalol /mg da amostra no extrato preparado por percolação e teor de flavonoides totais, que por sua vez apresentou um resultado de 17,1 ± 1,4 µg/mg de extrato. O extrato apresentou proteção da mucosa gástrica e este efeito pode estar relacionado à presença dos polifenóis e flavonóides encontrados

ABSTRACT Gastro protective activity of the Pavonia alnifolia A.St.-Hil. extract. In Brazil, the Malvaceae family is represented by at about 200 species. Some of those species are known as gastro protective ones. The Pavonia alnifolia A.St.-Hil (Malvaceae) was selected after a chemosystematic approach. The gastro preventive activity of the ethanol extract of stems Pavonia alnifolia was evaluated through the use of the Ethanol:chlroridric acid model on mice. The quantification of the total flavonoids (aluminum chloride method) and total polyphenols (Folin-Ciocalteu method) was also performed since the relation of those components with gastric protection has been previously highlighted. The tests showed a significant reduction of the ulcer formation in the mice treated with the plant extract (10, 100 and 300 mg/kg). This effect may be related to the presence of polyphenols whose content was found to be 74.3 ± 7.5 µg/mg of vegetal material and 82.7 ± 7.1 µg/mg of crude extract and flavonoids, which in turn showed a content of 17.1 ± 1.4 µg/mg dry extract

The chronic blockade of angiotensin I-converting enzyme eliminates the sex differences of serum cytokine levels of spontaneously hypertensive rats.

Sex hormones modulate the action of both cytokines and the renin-angiotensin system. However, the effects of angiotensin I-converting enzyme (ACE) on the proinflammatory and anti-inflammatory cytokine levels in male and female spontaneously hypertensive rats (SHR) are unclear. We determined the relationship between ACE activity, cytokine levels and sex differences in SHR. Female (F) and male (M) SHR were divided into 4 experimental groups each (n = 7): sham + vehicle (SV), sham + enalapril (10 mg/kg body weight by gavage), castrated + vehicle, and castrated + enalapril. Treatment began 21 days after castration and continued for 30 days. Serum cytokine levels (ELISA) and ACE activity (fluorimetry) were measured. Male rats exhibited a higher serum ACE activity than female rats. Castration reduced serum ACE in males but did not affect it in females. Enalapril reduced serum ACE in all groups. IL-10 (FSV = 16.4 ± 1.1 pg/mL; MSV = 12.8 ± 1.2 pg/mL), TNF-α (FSV = 16.6 ± 1.2 pg/mL; MSV = 12.8 ± 1 pg/mL) and IL-6 (FSV = 10.3 ± 0.2 pg/mL; MSV = 7.2 ± 0.2 pg/mL) levels were higher in females than in males. Ovariectomy reduced all cytokine levels and orchiectomy reduced IL-6 but increased IL-10 concentrations in males. Castration eliminated the differences in all inflammatory cytokine levels (IL-6 and TNF-α) between males and females. Enalapril increased IL-10 in all groups and reduced IL-6 in SV rats. In conclusion, serum ACE inhibition by enalapril eliminated the sexual dimorphisms of cytokine levels in SV animals, which suggests that enalapril exerts systemic anti-inflammatory and anti-hypertensive effects.

The chronic blockade of angiotensin I-converting enzyme eliminates the sex differences of serum cytokine levels of spontaneously hypertensive rats

Sex hormones modulate the action of both cytokines and the renin-angiotensin system. However, the effects of angiotensin I-converting enzyme (ACE) on the proinflammatory and anti-inflammatory cytokine levels in male and female spontaneously hypertensive rats (SHR) are unclear. We determined the relationship between ACE activity, cytokine levels and sex differences in SHR. Female (F) and male (M) SHR were divided into 4 experimental groups each (n = 7): sham + vehicle (SV), sham + enalapril (10 mg/kg body weight by gavage), castrated + vehicle, and castrated + enalapril. Treatment began 21 days after castration and continued for 30 days. Serum cytokine levels (ELISA) and ACE activity (fluorimetry) were measured. Male rats exhibited a higher serum ACE activity than female rats. Castration reduced serum ACE in males but did not affect it in females. Enalapril reduced serum ACE in all groups. IL-10 (FSV = 16.4 ± 1.1 pg/mL; MSV = 12.8 ± 1.2 pg/mL), TNF-α (FSV = 16.6 ± 1.2 pg/mL; MSV = 12.8 ± 1 pg/mL) and IL-6 (FSV = 10.3 ± 0.2 pg/mL; MSV = 7.2 ± 0.2 pg/mL) levels were higher in females than in males. Ovariectomy reduced all cytokine levels and orchiectomy reduced IL-6 but increased IL-10 concentrations in males. Castration eliminated the differences in all inflammatory cytokine levels (IL-6 and TNF-α) between males and females. Enalapril increased IL-10 in all groups and reduced IL-6 in SV rats. In conclusion, serum ACE inhibition by enalapril eliminated the sexual dimorphisms of cytokine levels in SV animals, which suggests that enalapril exerts systemic anti-inflammatory and anti-hypertensive effects.

Atividade antimutagênica de Carica papaya L. pelo ensaio do micronúcleo in vivo / Antimutagenic activity of Carica papaya L. assayed in vivo by micronucleus test

Há poucas informações sobre o efeito tóxico in vivo do extrato etanólico das folhas de Carica papaya (ECP). Portanto, esse estudo caracteriza quimicamente ECP por meio de HPLC-RP e avalia a atividade antimutagênica e citotóxica da fração aquosa de ECP422 Antimutagenic activity of Carica papaya L.Rev Ciênc Farm Básica Apl., 2011;32(3):419-423(CA), empregando ensaio do micronúcleo (MN). O extrato tem predominância de substâncias polares, entre elas a rutina. O ensaio do MN foi realizado em ratos Wistar. Grupos: Controle Negativo (CN), veículo; Controle Positivo (CP40), ciclofosfamida (40 mg/Kg i.p.), 24 horas; Grupo tratado (CA), ECP (500 mg/Kg, p.p.) 24h; Grupo Tratado (CACP40), CA (500 mg/Kg, p.o.) 48, 36 e 24 horas , a última dose de ECP foi administrada junto com ciclofosfamida (40 mg/Kg, i.p.). O índice de MN para CN e CA foi de 3,2 ± 1,79 e 1,6 ± 0,5, e razão PCE/NCE foi de 1,38 ± 0,52 e 1,13 ± 0,28, respectivamente, indicando baixa toxicidade. Por outro lado o índice de MN foi de 20 ± 4,9 para CP40 e 3,0 ± 1,6 para o CACP40, indicando efeito antimutagênico de ECP. Este estudo sugere que ECP possui efeito antimutagênico e baixa toxicidade e que a rutina pode estar envolvida nesse efeito.

There is little information about in vivo toxic effects of the ethanolic extract of leaves of Carica papaya L. (ECP). Therefore, in this study ECP was characterized chemically by HPLC-RP and the antimutagenic and cytotoxic activities of an aqueous solution of ECP (CA) were assessed by the micronucleus (MN) bioassay. The extract consisted mainly of polar substances, one of which was rutin. The MN test was performed on groups of Wistar rats, as follows: negative control (NC) - vehicle; positive control (CP40) - cyclophosphamide (40 mg/kg, ip), 24h; extract-treated (CA) - ECP (500 mg/kg, po), 24h; extract + cyclophosphamide-treated (CACP40) - ECP (500 mg/kg, po), 48, 36 and 24 h, plus cyclophosphamide (40 mg/kg, ip), 24h. The MN index was 3.2 ± 1.79 and 1.6 ± 0.5, for NC and CA, and the PCE-to-NCE ratio was 1.38 ± 0.52 and 1.13 ± 0.28, respectively, indicating low cytotoxicity of CA. CP40 showed a high MN index of 20 ± 4.9, but CACP40 only 3.0 ± 1.6, the same as NC, indicating an antimutagenic effect. The study suggests that ECP has low toxicity and possesses an antimutagenic protective effect in which rutin may be involved.

Estudo químico e da atividade biológica cardiovascular do óleo essencial de folhas de Alpinia zerumbet (Pers.) B.L.Burtt & R.M.Sm. em ratos / Phytochemistry and cardiovascular biological activity of the essential oil from leaves of Alpinia zerumbet (Pers.) B.L. Burtt & R.M.Sm. in rats

A espécie vegetal Alpinia zerumbet (Pers.) B.L.Burtt & R.M. Sm. é popularmente empregada para o tratamento de diversas enfermidades, entre elas a hipertensão. Avaliar a composição química, a atividade antihipertensiva e ação na hipertrofia cardíaca do óleo essencial das folhas de Alpinia zerumbet (OEAZ) em ratos foram os objetivos deste estudo. O OEAZ, obtido por hidrodestilação em aparelho Clevenger, teve sua composição química analisada em cromatografia gasosa acoplada à espectrometria de massas (CG-EM). Foram identificados 14 constituintes, sendo terpinen-4-ol (37,45 por cento) o majoritário, seguido pelos óxido de cariofileno (7,56 por cento), trans-hidrato de sabineno (6,61 por cento) e 1,8-cineol (4,02 por cento). A avaliação cardiovascular foi feita após o tratamento crônico de ratos espontaneamente hipertensos (SHR) e seus respectivos controles, ratos Wistar-Kyoto (WKY). Os dados hemodinâmicos revelaram redução da pressão arterial média (PAM) no grupo tratado (SHRP: 160 ± 7 mm Hg; p<0,01) em relação ao não tratado (SHR: 180 ± 5 mm Hg). A relação entre peso do ventrículo esquerdo e peso corporal (VE/PC) do SHRP (2,50 ± 0,03 mg g-1; p<0,01) mostrou-se inferior ao SHR (2,61 ± 0,01 mg g-1), confirmando a redução da hipertrofia cardíaca (HC). Os dados de PAM e VE/PC dos animais SHRP foram estatisticamente diferentes quando comparados com os ratos controle (WKY: 116 ± 2 mm Hg e WKYP: 119 ± 4 mm Hg; p<0,05; WKY: 2,15 ± 0,04 mg g-1 e WKYP: 2,17 ± 0,04 mg g-1 ; p<0,01), indicando não ter havido normalização dos mesmos. Conclui-se que o tratamento crônico com OEAZ foi capaz de determinar redução, mas não a normalização, da PAM e da HC de ratos SHR, provavelmente pela presença dos componentes terpinen-4-ol e 1,8-cineol. Estudos com doses maiores ou período de tratamento superior são necessários para avaliar a possibilidade de o OEAZ normalizar os parâmetros analisados (PAM e HC).

Alpinia zerumbet (Pers.) B.L. Burtt & R.M.Sm. is traditionally employed to treat several diseases such as hypertension. The aim of this study was to evaluate the chemical composition, the anti-hypertensive activity and the capacity to reduce cardiac hypertrophy of the essential oil of A. zerumbet leaves (EOAZ) in rats. EOAZ was obtained through hydrodistillation in Clevenger apparatus and its chemical composition was analyzed by gas chromatography-mass spectrometry (GC-MS). Several constituents (14) were identified, terpen-4-ol (37.45 percent) being the major component, followed by caryophyllene oxide (7.56 percent), trans-sabinene hydrate (6.61 percent) and 1,8-cineol (4.02 percent). The cardiovascular effect was investigated after chronic treatment with spontaneously hypertensive rats (SHR) and their respective controls, Wistar-Kyoto rats (WKY). The treated group showed a lower mean arterial pressure (MAP) (SHRP: 160 ± 7 mm Hg; p<0.01) than the untreated group (SHR: 180 ± 5 mm Hg). The ratio of left ventricle-to-body weight (LV/BW) for SHRP was lower (2.504 ± 0.03 mg g-1; p<0.01) than that for SHR (2.162 ± 0.01 mg g-1), confirming the cardiac hypertrophy (CH) reduction. There were significant differences in MAP and CH between SHRP animals and control rats (WKY: 116 ± 2 mm Hg and WKYP: 119 ± 4 mm Hg; p<0.05. WKY: 2.152 ± 0.04 mg g-1 and WKYP: 2.168 ± 0.04 mg g-1; p<0.01), indicating that these values were not normalized. Those data showed that the chronic treatment with EOAZ reduces MAP and CH in SHR probably due to the presence of the compounds terpinen-4-ol and 1,8-cineol. Studies with higher doses or longer treatment periods are necessary to evaluate whether EOAZ can reduce the analyzed parameters (MAP and CH) to normal values.

Influence of renal denervation on blood pressure, sodium and water excretion in acute total obstructive apnea in rats.

Obstructive apnea (OA) can exert significant effects on renal sympathetic nerve activity (RSNA) and hemodynamic parameters. The present study focuses on the modulatory actions of RSNA on OA-induced sodium and water retention. The experiments were performed in renal-denervated rats (D; N = 9), which were compared to sham (S; N = 9) rats. Mean arterial pressure (MAP) and heart rate (HR) were assessed via an intrafemoral catheter. A catheter was inserted into the bladder for urinary measurements. OA episodes were induced via occlusion of the catheter inserted into the trachea. After an equilibration period, OA was induced for 20 s every 2 min and the changes in urine, MAP, HR and RSNA were recorded. Renal denervation did not alter resting MAP (S: 113 +/- 4 vs D: 115 +/- 4 mmHg) or HR (S: 340 +/- 12 vs D: 368 +/- 11 bpm). An OA episode resulted in decreased HR and MAP in both groups, but D rats showed exacerbated hypotension and attenuated bradycardia (S: -12 +/- 1 mmHg and -16 +/- 2 bpm vs D: -16 +/- 1 mmHg and 9 +/- 2 bpm; P < 0.01). The basal urinary parameters did not change during or after OA in S rats. However, D rats showed significant increases both during and after OA. Renal sympathetic nerve activity in S rats increased (34 +/- 9%) during apnea episodes. These results indicate that renal denervation induces elevations of sodium content and urine volume and alters bradycardia and hypotension patterns during total OA in unconscious rats.

Influence of renal denervation on blood pressure, sodium and water excretion in acute total obstructive apnea in rats

Obstructive apnea (OA) can exert significant effects on renal sympathetic nerve activity (RSNA) and hemodynamic parameters. The present study focuses on the modulatory actions of RSNA on OA-induced sodium and water retention. The experiments were performed in renal-denervated rats (D; N = 9), which were compared to sham (S; N = 9) rats. Mean arterial pressure (MAP) and heart rate (HR) were assessed via an intrafemoral catheter. A catheter was inserted into the bladder for urinary measurements. OA episodes were induced via occlusion of the catheter inserted into the trachea. After an equilibration period, OA was induced for 20 s every 2 min and the changes in urine, MAP, HR and RSNA were recorded. Renal denervation did not alter resting MAP (S: 113 ± 4 vs D: 115 ± 4 mmHg) or HR (S: 340 ± 12 vs D: 368 ± 11 bpm). An OA episode resulted in decreased HR and MAP in both groups, but D rats showed exacerbated hypotension and attenuated bradycardia (S: -12 ± 1 mmHg and -16 ± 2 bpm vs D: -16 ± 1 mmHg and 9 ± 2 bpm; P < 0.01). The basal urinary parameters did not change during or after OA in S rats. However, D rats showed significant increases both during and after OA. Renal sympathetic nerve activity in S rats increased (34 ± 9 percent) during apnea episodes. These results indicate that renal denervation induces elevations of sodium content and urine volume and alters bradycardia and hypotension patterns during total OA in unconscious rats.

Efeito da administração do Allium sativum sobre as alterações cardiovasculares de ratos Wistar com infarto do miocárdio. / Effects of consumption of Allium sativum on the cardiovascular abnormalities observed in Wistar rats following cardiac infarction.

O alho (Allium sativum) apresenta várias ações benéficas ao sistema circulatório, tais como diminuição dos níveis de colesterol total, LDL-colesterol e da pressão arterial, além de efeito antioxidante. O objetivo deste estudo foi avaliar o efeito da administração do Allium sativum sobre as alterações da hemodinâmica cardiovascular e estruturais macroscópicas do coração de animais com infarto induzido experimentalmente. Ratos Wistar foram tratados, previamente e após indução do infarto, com homogeneizado de alho na dose de 125mg/Kg/dia durante 21 dias, por via oral (uma semana antes e duas depois do procedimento de infarto). Os grupos controle passaram por cirurgia fictícia (SHAM). Os animais foram divididos em grupos controles e infartados com (SHAMT, INFT; respectivamente) ou sem (SHAM, INF; respectivamente) tratamento com alho. Houve redução da hipertrofia do ventrículo direito (INF=0,75±0,05 vs. INFT=0,61±0,03 mg/Kg; p<0,01), da área de infarto (INF=29,7±4,8% vs. INFT=20,4±1,4%; p<0,05) e regularização dos níveis de pressão arterial sistólica (PAS; INF=100±8 vs. INFT=127±7 mmHg; p<0,05) e média (PAM; INF=94±4 vs. INFT=110±6 mmHg; p<0,01) dos animais INFT comparados com os INF. Houve um menor número de animais mortos após o procedimento de infarto no grupo INFT em relação ao grupo INF (20%, n=2; 45,5%, n=5; respectivamente). Esses achados indicam que o alho tem um importante papel na prevenção e no controle de alterações cardiovasculares, uma vez que houve redução do número de mortes pós-infarto e melhor perfil cardiovascular dos animais INFT.

Garlic (Allium sativum) has several beneficial effects on the cardiovascular system, such as reductions of the levels of total cholesterol, LDL-cholesterol and blood pressure, besides acting as an antioxidant. The aim of this study was to assess the effects of administering Allium sativum on changes in the cardiovascular hemodynamics and macroscopic structure that occur in the hearts of animals with experimentally induced cardiac infarction. Male Wistar rats were treated with homogenized garlic at a dose of 125mg/kg b.w./day for 21 days, given orally for one week before and two weeks after the procedure to induce myocardial infarction. The control group was subjected to a fictitious surgery (SHAM). The animals were divided into control and infarcted groups, treated (SHAMT, INFT) or untreated (SHAM, INF) with garlic. There were reductions in right ventricular hypertrophy (INF=0.75±0.05 vs. INFT=0.61±0.03 mg.kg-1; p<0.01) and infarcted area (INF=29.7±4.8 % vs. INFT=20.4±1.4 %; p<0.05) and regularization of the levels of systolic (SAP; INF=100±8 vs. INFT=127±7 mm Hg; p<0.05) and mean arterial pressure (MAP; INF=94±4 vs. INFT=110±6 mm Hg; p<0.01) in the INFT animals, compared to the INF group. Fewer animals died after the cardiac infarction procedure in the group INFT than in INF (20%, n=2; 45.5%, n=5; respectively). These findings suggest that garlic can have an important role in the prevention and control of cardiovascular abnormalities, since there was a reduction in the number of post-infarction deaths and an improvement of the cardiovascular profile in the INFT animals.

Effect of enalapril treatment on the sensitivity of cardiopulmonary reflexes in rats with myocardial infarction.

1. The aim of the present study was to evaluate the effect of treatment with enalapril on the sensitivity of cardiopulmonary reflexes 30 days after myocardial infarction in Wistar rats. 2. Animals were divided into four groups: (i) sham operated, receiving vehicle (SHAM); (ii) infarcted, receiving vehicle (0.9% NaCl; INF); (iii) sham operated, receiving enalapril (SHAME); and (iv) infarcted, receiving enalapril (INFE). 3. Enalapril was administered at a dose of 10 mg/kg per day. Serotonin (4-32 microg/kg, i.v.) was administered in order to activate the Bezold-Jarisch reflex, which was estimated as the percentage of reduction in heart rate. 4. The volume-sensitive cardiopulmonary reflex was induced by saline overload and evaluated as the percentage increase in sodium and volume renal excretion. At the end of the experiments, rats were killed and hearts excised to estimate the size of the infarction. The weight of the kidneys, lungs, liver and cardiac chambers as ratios of bodyweight was used to estimate the extent of hypertrophy. 5. The results showed an impairment in the sensitivity of the cardiopulmonary reflexes in the INF group compared with the SHAM and SHAME groups. We observed right ventricle and pulmonary hypertrophy, a reduction in mean and systolic arterial pressure and an increase in heart rate in INF animals. In the INFE group, nearly all the parameters were normal compared with the INF group, except for systolic arterial pressure, which was only partially improved. 6. The main finding of the present study was that treatment with enalapril normalized the sensitivity of the cardiopulmonary reflexes, which could be due, in part, to the reduction of cardiac hypertrophy. The present study provides information about the beneficial effects of the angiotensin-converting enzyme inhibitors by normalizing the cardiopulmonary reflexes involved with the regulation of volume and sodium, as well as control of arterial pressure and heart rate in infarcted animals.