Impact of hypotensive action of angiotensin converting enzyme inhibitor on ovarian-intraovarian blood flow and follicles development in goats hormonally stimulated with repeated FSH-ECG treatment

Background: Recent evidence shows that the renin-angiotensin system (RAS) participates in important reproductiveprocesses, such as steroidogenesis, folliculogenesis, oocyte maturation and ovulation. Several studies have proposed touse an angiotensin-converting enzyme (ACE) as a RAS modulator, aiming to improve reproductive efficiency, however,the presence of the main components of this system in reproductive tissues still need to be further investigated, since thephysiological functions seem to be species-specific. The aim of this study was to assess the impact of enalapril-maleate,an ACE inhibitor, during repeated gonadotropins treatment on ovarian blood flow and follicular development in goats.Materials, Methods & Results: Twenty Anglo-Nubian cross-bred goats were equally grouped according to parity (n= 10/group): nulliparous and multiparous parity. In each group, five animals were randomly selected to receive 0.4 mg.kg-1 ofenalapril-maleate during 11 days of estrus synchronization and gonadotropins treatments. The other animals received thesame volume of saline solution. Estrus synchronization of all goats was made by intramuscular ad-ministration of PGF2αanalog, followed 48 h later by intravaginal insertion of a controlled internal drug release device. Forty-eight h after devicewithdrawal, a single dose of 60 mg of FSH plus 300 UI of eCG was administered and repeated every 4 days to complete 3treatments. Transrectal ultrasonography was performed using pulsed and color Doppler to evaluate Doppler velocimetricsparameters of the ovarian artery and intraovarian blood flow, respec-tively, and B-mode real-time ultrasound scanner toevaluate the follicular development. In the females treated with enalapril-maleate was observed a significant reduction ofsystolic and diastolic peak, without difference according to parity. In addition, in the third session of hor-monal stimulation,only the groups (nulliparous and multiparous) not treated with...(AU)

Impact of hypotensive action of angiotensin converting enzyme inhibitor on ovarian-intraovarian blood flow and follicles development in goats hormonally stimulated with repeated FSH-ECG treatment

Background: Recent evidence shows that the renin-angiotensin system (RAS) participates in important reproductiveprocesses, such as steroidogenesis, folliculogenesis, oocyte maturation and ovulation. Several studies have proposed touse an angiotensin-converting enzyme (ACE) as a RAS modulator, aiming to improve reproductive efficiency, however,the presence of the main components of this system in reproductive tissues still need to be further investigated, since thephysiological functions seem to be species-specific. The aim of this study was to assess the impact of enalapril-maleate,an ACE inhibitor, during repeated gonadotropins treatment on ovarian blood flow and follicular development in goats.Materials, Methods & Results: Twenty Anglo-Nubian cross-bred goats were equally grouped according to parity (n= 10/group): nulliparous and multiparous parity. In each group, five animals were randomly selected to receive 0.4 mg.kg-1 ofenalapril-maleate during 11 days of estrus synchronization and gonadotropins treatments. The other animals received thesame volume of saline solution. Estrus synchronization of all goats was made by intramuscular ad-ministration of PGF2αanalog, followed 48 h later by intravaginal insertion of a controlled internal drug release device. Forty-eight h after devicewithdrawal, a single dose of 60 mg of FSH plus 300 UI of eCG was administered and repeated every 4 days to complete 3treatments. Transrectal ultrasonography was performed using pulsed and color Doppler to evaluate Doppler velocimetricsparameters of the ovarian artery and intraovarian blood flow, respec-tively, and B-mode real-time ultrasound scanner toevaluate the follicular development. In the females treated with enalapril-maleate was observed a significant reduction ofsystolic and diastolic peak, without difference according to parity. In addition, in the third session of hor-monal stimulation,only the groups (nulliparous and multiparous) not treated with...

Efeito de um inibidor da Enzima Conversora de Angiotensina sobre a esteroidogênese, e Angiotensina II e Angiotensina-(1-7) em cabras superovuladas / Effect of an angiotensin-converting enzyme inhibitor on steroidogenesis, angiotensin II and angiotensin-(1-7) in superovulated goats

Local renin angiotensin (RAS) system has been described in the ovary, which has been implicated invarious reproductive functions. To evaluate the ovarian RAS in, 13 goats were randomly divided into two groups:Enalapril (n = 7) and control (n = 6). Then, they received superovulation protocol. Enalapril further groupreceived subcutaneously (2mg/kg) enalapril maleate (0.4 mg/kg/day). Blood samples were collected on days 3, 6, 9and 11, and follicular fluid samples from pre-ovulatory ovarian follicles after exposure by celiotomy on D11. AngII in serum and follicular fluid were evaluated on days 9 and 12, Ang-(1-7) on day 12 by HPLC and RIA. E2 andP4 concentrations in serum were determined by ELISA. Ang-(1-7) concentrations in plasma was greater on day9 (P < 0.05), important period for the recruitment and follicular selection. This may indicate that these peptidescan an important function in follicular development and oocyte maturation in superovulated goats.(AU)

Efeito de um inibidor da Enzima Conversora de Angiotensina sobre a esteroidogênese, e Angiotensina II e Angiotensina-(1-7) em cabras superovuladas / Effect of an angiotensin-converting enzyme inhibitor on steroidogenesis, angiotensin II and angiotensin-(1-7) in superovulated goats

Local renin angiotensin (RAS) system has been described in the ovary, which has been implicated invarious reproductive functions. To evaluate the ovarian RAS in, 13 goats were randomly divided into two groups:Enalapril (n = 7) and control (n = 6). Then, they received superovulation protocol. Enalapril further groupreceived subcutaneously (2mg/kg) enalapril maleate (0.4 mg/kg/day). Blood samples were collected on days 3, 6, 9and 11, and follicular fluid samples from pre-ovulatory ovarian follicles after exposure by celiotomy on D11. AngII in serum and follicular fluid were evaluated on days 9 and 12, Ang-(1-7) on day 12 by HPLC and RIA. E2 andP4 concentrations in serum were determined by ELISA. Ang-(1-7) concentrations in plasma was greater on day9 (P < 0.05), important period for the recruitment and follicular selection. This may indicate that these peptidescan an important function in follicular development and oocyte maturation in superovulated goats.

Enalapril e captopril revertem o edema e a hiperplasia renais causados pelo antimoniato de N-metilglucamina em camundongos C57BL/6 / Enalapril and captopril reverse edema and renal hyperplasia caused by N-methylglucamine antimonate in C57BL/6 mice

The aim of this study was to verify whether enalapril and captopril would reverse the renal damage caused by N-methylglucamine antimoniate in C57BL/6 mice. We used inbred C57BL/6 female mice, obtained from the Oswaldo Cruz Foundation (FIOCRUZ), Salvador, BA. The mice were divided into four groups as follows: Group1: received saline by the intramuscular (IM) route; Group 2: received N-methylglucamine antimonate (IM); Group 3: received N-methylglucamine antimoniate and captopril; Group 4: was treated with N-methylglucamine antimoniate and enalapril. Both enalapril and captopril were orally administered in drinking water (ad libitum). After 30 days of treatment, the animals were sacrificed and their kidneys were collected for histological analysis which showed that enalapril completely reversed the edema, the podocytes hyperplasia and nucleus of the epithelial cells in the proximal convoluted tubules caused by N-methylglucamine antimoniate. On the other hand, the captopril treatment partially inhibited kidney harmful effects caused by N-metilgucamina antimoniate. Taken together, we would conclude that enalapril and captopril reverse edema and renalhyperplasia caused by N-methylglucamine antimonate in mice.(AU)

Enalapril e captopril revertem o edema e a hiperplasia renais causados pelo antimoniato de N-metilglucamina em camundongos C57BL/6 / Enalapril and captopril reverse edema and renal hyperplasia caused by N-methylglucamine antimonate in C57BL/6 mice

The aim of this study was to verify whether enalapril and captopril would reverse the renal damage caused by N-methylglucamine antimoniate in C57BL/6 mice. We used inbred C57BL/6 female mice, obtained from the Oswaldo Cruz Foundation (FIOCRUZ), Salvador, BA. The mice were divided into four groups as follows: Group1: received saline by the intramuscular (IM) route; Group 2: received N-methylglucamine antimonate (IM); Group 3: received N-methylglucamine antimoniate and captopril; Group 4: was treated with N-methylglucamine antimoniate and enalapril. Both enalapril and captopril were orally administered in drinking water (ad libitum). After 30 days of treatment, the animals were sacrificed and their kidneys were collected for histological analysis which showed that enalapril completely reversed the edema, the podocytes hyperplasia and nucleus of the epithelial cells in the proximal convoluted tubules caused by N-methylglucamine antimoniate. On the other hand, the captopril treatment partially inhibited kidney harmful effects caused by N-metilgucamina antimoniate. Taken together, we would conclude that enalapril and captopril reverse edema and renalhyperplasia caused by N-methylglucamine antimonate in mice.(AU)

Angiotensin-converting enzyme inhibitors of Bothrops jararaca snake venom affect the structure of mice seminiferous epithelium

Background Considering the similarity between the testis-specific isoform of angiotensin-converting enzyme and the C-terminal catalytic domain of somatic ACE as well as the structural and functional variability of its natural inhibitors, known as bradykinin-potentiating peptides (BPPs), the effects of different synthetic peptides, BPP-10c (<ENWPHQIPP), BPP-11e (<EARPPHPPIPP), BPP-AP (<EARPPHPPIPPAP) and captopril were evaluated in the seminiferous epithelium of male mice.Methods The adult animals received either one of the synthetic peptides or captopril (120 nmol/dose per testis) via injection into the testicular parenchyma. After seven days, the mice were sacrificed, and the testes were collected for histopathological evaluation.Results BPP-10c and BPP-AP showed an intense disruption of the epithelium, presence of atypical multinucleated cells in the lumen and high degree of seminiferous tubule degeneration, especially in BPP-AP-treated animals. In addition, both synthetic peptides led to a significant reduction in the number of spermatocytes and round spermatids in stages I, V and VII/VIII of the seminiferous cycle, thickness of the seminiferous epithelium and diameter of the seminiferous tubule lumen. Interestingly, no morphological or morphometric alterations were observed in animals treated with captopril or BPP-11e.Conclusions The major finding of the present study was that the demonstrated effects of BPP-10c and BPP-AP on the seminiferous epithelium are dependent on their primary structure and cannot be extrapolated to other BPPs.(AU)

Pimobendan improves clinical signs in short term compared to digoxin or placebo in dogs with heart failure due to chronic degenerative mitral valve disease

Background: Chronic degenerative mitral valve disease (CDMVD) continues to be the most common cause of heart failure (HF) in small breed dogs. Pimobendan (PIMO) is a mixed action drug with inotropic and vasodilator properties and is widely used to treat heart disease in dogs. Therefore, PIMO increases cardiac output, reduces both preload and afterload and increases myocardial contractility without increasing energy consumption and myocardial oxygen. Digoxin (DIG) is a cardiac glycoside acting through inhibition of the sarcolemmal Na+/K+ ATPase pump, hence increasing intracellular calcium. It exerts beneficial effects on left ventricular function, symptoms and exercise tolerance. The purpose of this prospective, randomized, double blind clinical trial was to evaluate the clinical response and QoLQ in heart failure (HF) dogs treated with digoxin or pimobendan in addition to conventional therapy (furosemide and benazepril).Materials, Methods & Results: Inclusion criteria: dogs in class III or stabilized class IV (NYHA). Exclusion criteria: use of positive inotrope and antiarrhythmic, presence of atrial fibrillation, renal or hepatic disease or neoplasia. Thirty three dogs were included and randomly assigned to DIG (n = 11), PIMO (n = 14) and placebo (PL) (n = 8) and followed up weekly. Data was evaluated for days zero, 7, 14 and 28. Increasing score was assigned to...(AU)

Pimobendan improves clinical signs in short term compared to digoxin or placebo in dogs with heart failure due to chronic degenerative mitral valve disease

Background: Chronic degenerative mitral valve disease (CDMVD) continues to be the most common cause of heart failure (HF) in small breed dogs. Pimobendan (PIMO) is a mixed action drug with inotropic and vasodilator properties and is widely used to treat heart disease in dogs. Therefore, PIMO increases cardiac output, reduces both preload and afterload and increases myocardial contractility without increasing energy consumption and myocardial oxygen. Digoxin (DIG) is a cardiac glycoside acting through inhibition of the sarcolemmal Na+/K+ ATPase pump, hence increasing intracellular calcium. It exerts beneficial effects on left ventricular function, symptoms and exercise tolerance. The purpose of this prospective, randomized, double blind clinical trial was to evaluate the clinical response and QoLQ in heart failure (HF) dogs treated with digoxin or pimobendan in addition to conventional therapy (furosemide and benazepril).Materials, Methods & Results: Inclusion criteria: dogs in class III or stabilized class IV (NYHA). Exclusion criteria: use of positive inotrope and antiarrhythmic, presence of atrial fibrillation, renal or hepatic disease or neoplasia. Thirty three dogs were included and randomly assigned to DIG (n = 11), PIMO (n = 14) and placebo (PL) (n = 8) and followed up weekly. Data was evaluated for days zero, 7, 14 and 28. Increasing score was assigned to...

The effect of anti-hypertensive drugs on the obstructive pancreatitis in rats / Efeitos de fármacos anti-hipertensivos sobre pancreatite obstrutiva em ratos

PURPOSE: To investigate the effect of ACE inhibitor, lisinopril and AT1 blocker, losartan, on the obstructive pancreatitis in rat. METHODS: Acute pancreatitis in rats (n=21) was induced for a common hepatic duct were ligated proximal to its entry into the pancreas and the common bile - pancreatic duct were also ligated near its junction with the duodenum, under ether anesthesia, after which the abdomen were closed. The animals was divided in tree groups, being two treated and control group. The animals was treated with Losartan and Lisinopril at the dose of 10µg/Kg body weight per day, i.p., in a proportional volume, for five days, before and after treatement. RESULTS: The inflammation, collagen deposition in the pancreas of treated animals were smaller, suggesting that the use of antihypertensive agents interfered positively in the depletion of the injury of the pancreas. Scythe showed a correlation between activity of pancreatic stellate cells (PSCs) lower in treated animals when compared to control. CONCLUSION: The pancreatic stellate cells strength are involved in collagen production during acute pancreatitis and why antihypertensive drugs such as lisinopril and losartan may possibly have beneficial effects in reducing pancreatic fibrosis in models of experimental obstructive pancreatitis.(AU)

OBJETIVO: Investigar o efeito de um inibidor da ECA, lisinopril e bloqueador AT1, losartan, a pancreatite obstrutiva em ratos. MÉTODOS: Pancreatite aguda em ratos (n = 21) foi induzida por um ducto hepático comum foram ligados proximal à sua entrada no pâncreas e da bílis comum - ducto pancreático também foram ligados perto de sua junção com o duodeno, sob anestesia com éter, após o que abdome foram fechadas. Os animais foram divididos em três grupos, sendo dois tratados eo grupo controle. Os animais foram tratados com lisinopril e losartan na dose de 10µg/Kg de peso corporal por dia, IP, em um volume proporcional, por cinco dias, antes e depois do tratamento com. RESULTADOS: A inflamação, deposição de colágeno no pâncreas de animais tratados foram menores, sugerindo que o uso de agentes anti-hipertensivos interferiram positivamente na diminuição da lesão do pâncreas. Este estudo mostrou uma correlação entre a atividade das células pancreáticas estreladas (CSP) menor nos animais tratados quando comparados ao control. CONCLUSÃO: A força das células pancreáticas estreladas está envolvida na produção de colágeno durante a pancreatite aguda e por medicamentos anti-hipertensivos, tais como lisinopril e losartan pode eventualmente ter efeitos benéficos na redução da fibrose do pâncreas em modelos experimentais de pancreatite obstrutiva.(AU)

Tratamento de insuficiência cardíaca com benazepril em cães com cardiomiopatia dilatada e endocardiose / Treatment of congestive heart failure with benazepril in dogs with dilated cardiomyopathy and endocardiosis

Foram avaliados os efeitos clínicos do benazepril, um inibidor da enzima de conversão da angiotensina de ação prolongada, em cães com insuficiência cardíaca congestiva (ICC) secundária à endocardiose de mitral ou cardiomiopatia dilatada. O medicamento foi administrado na dose de 0,25 a 0,5mg/kg/dia. Diuréticos, digitálicos e fármacos antiarrítmicos foram usados de acordo com a necessidade de cada paciente. Exames físico, radiográfico e eletrocardiográfico foram realizados nos dias 0, 7, 28 e 56. A gasometria arterial e a bioquímica sérica foram avaliadas nos dias 0 e 56. Os sinais de dispnéia e o estado geral dos pacientes melhoraram em todos os cães após o início do tratamento. Houve diminuição na freqüência da tosse e não houve alterações no eletrocardiograma, exceto pela diminuição na amplitude e na duração da onda P. Nenhum efeito colateral foi observado. Conclui-se que o benazepril é um inibidor da enzima de conversão da angiotensina, eficaz e bem tolerado no tratamento da ICC no cão.(AU)

Clinical effects of benazepril, a long acting angiotensin-converting enzyme (ACEi), in dogs with naturally-occurring congestive heart failure (CHF) caused by mitral endocardiosis or dilated cardiomyopathy were studied. The drug was given orally at a dose of 0.25 to 0.5mg/kg/day. Diuretics, digitalics, and antiarrhtyhmic drugs were given as needed. Physical, radiographic, and eletrocardiographic examination were performed at days 0, 7, 28, and 56. Serum biochemistry and arterial blood gases were obtained at days 0 and 56. Signs of dyspnea and general condition improved in all dogs. Cough decreased in frequency. The electrocardiogram did not change with benazepril use except for a decrease in P wave amplitude and duration. No adverse effects related to the use of benazepril were observed. Benazepril is an effective and well tolerated ACEi for the treatment of CHF in dogs.(AU)