BJ-PRO-7A and BJ-PRO-10C induce vasodilatation and inotropic effects in normotensive and hypertensive rats: Role of nitric oxide and muscarinic receptors.

Bj-PRO-7a and Bj-PRO-10c belong to a family of proline-rich oligopeptides (PROs) identified in Bothrops jararaca (Bj) crude venom. Previous studies have shown an antihypertensive effect evoked by theses peptides. However, the mechanisms underlying the direct effects on vessels and heart remain to be unraveled. Thus, we investigated the effect of the Bj-PRO-7a and Bj-PRO-10c in the aorta and coronary arteries and in cardiac contractility in normotensive (Wistar) and hypertensive (SHR) rats. Pre-constricted aortic rings were exposed to increasing concentrations of Bj-PROs in presence or absence of muscarinic type 1 receptor antagonist (Pirenzepine), nonselective muscarinic receptor antagonist (Atropine), nitric oxide synthase inhibitor (L-NAME), guanylyl cyclase inhibitor (ODQ), adenylyl cyclase inhibitor (MDL), or argininosuccinate synthetase inhibitor (MDLA). The effects of Bj-PROs in the cardiac contractility and coronary vasomotricity were evaluated using Langendorff perfused heart preparation. The rat hearts were perfused with Bj-PRO-7a or Bj-PRO-10c in absence or presence of L-NAME, ODQ or MDL. Both Bj-PROs induced endothelium-dependent vasorelaxation in aortic rings from Wistars and SHRs. These effects were inhibited by L-NAME, ODQ or MDL. Atropine and Pirenzepine blocked the vasorelaxant effect of Bj-PRO-7a in aorta from both strains. MDLA inhibited the Bj-PRO-10c-induced vasorelaxation in aortic rings from SHR, but not Wistar. The Bj-PRO-7a induced coronary vasodilation only in SHR. L-NAME, ODQ and MDL inhibited this effect. Bj-PRO-10c induced coronary vasodilatation in both strains, which was blocked by L-NAME, ODQ and MDL. Bj-PRO-7a decreased the dP/dt max in Wistar hearts and the dP/dt min in Wistar and SHR hearts. These effects were abolished by L-NAME. Bj-PRO-10c decreased dP/dt max and dP/dt min in hearts from normotensive and hypertensive animals, which were abolished in the presence of L-NAME, MDL and ODQ. In summary, the Bj-PROs induced endothelium-dependent vasorelaxation in rat thoracic aorta, coronary vasodilation and negative inotropic effects through mechanisms mediated by activation of nitric oxide pathway.

Influence of antihypertensive drugs on aortic and coronary effects of Ang-(1-7) in pressure-overloaded rats.

This study investigated the influence of antihypertensive drugs, such as angiotensin-converting enzyme inhibitors (ACEIs), AT1 receptor blockers (ARBs), voltage-gated L-type calcium channel blockers, and mineralocorticoid receptor antagonists (MRAs), on the effects of angiotensin-(1-7) [Ang-(1-7)] on aorta and coronary arteries from pressure-overloaded rats. Pressure overload was induced by abdominal aortic banding (AB). To evaluate the role of antihypertensive drugs on the effect of Ang-(1-7), AB male Wistar rats weighing 250-300 g were treated with vehicle or low doses (5 mg·kg-1·day-1, gavage) of losartan, captopril, amlodipine, or spironolactone. Isolated aortic rings and isolated perfused hearts under constant flow were used to evaluate the effect of Ang-(1-7) in thoracic aorta and coronary arteries, respectively. Ang-(1-7) induced a significant relaxation in the aorta of sham animals, but this effect was reduced in the aortas of AB rats. Chronic treatments with losartan, captopril or amlodipine, but not with spironolactone, restored the Ang-(1-7)-induced aorta relaxation in AB rats. The coronary vasodilatation evoked by Ang-(1-7) in sham rats was blunted in hypertrophic rats. Only the treatment with losartan restored the coronary vasodilatory effect of Ang-(1-7) in AB rat hearts. These data support a beneficial vascular effect of an association of Ang-(1-7) and some antihypertensive drugs. Thus, this association may have potential as a new therapeutic strategy for cardiovascular diseases.

Effects of protein malnutrition on muscle fibers of the brachial biceps and medial pterygoid of Wistar rats

Protein malnutrition is a public health problem, and in childhood, it can lead to muscle deficits. Here, our objective was to evaluate the effects of malnutrition upon the muscle fibers in the medial pterygoid and braquial biceps. Ten just weaned rat pups that had been born to parents fed a nourished or malnourished diet (N = 5 per group) were studied. The medial pterygoid and braquial biceps muscles were removed and crosssectioned, and histological staining with picrosirius and histochemistry reaction with nicotinamide adenine dinucleotide - tetrazolium reductase (NADH-tr) were performed. The samples stained with picrosirius were observed under polarized light, and from the qualitative analysis, we observed that type I collagen fibers were only present in the braquial biceps muscles of the nourished animals. The NADH-tr reaction indicated that the pterygoid muscle specimens from the malnourished pups lacked intermediate muscle fibers. The crosssectional area of the muscle was lower in the malnourished group than in the nourished group. The density of muscle fibers was higher in the malnourished group than in the nourished group. The consequences of malnutrition were visible when comparing the muscles. We concluded that the differences in daily muscle action along with the differences in embryological origin are instrumental in establishing the results.

Controle biológico de tricostrongilídeos (Nematoda: Trichostrongyloidea) gastrintestinais de bovinos pelo fungo Monacrosporium sinense / Biological control of gastrointestinal trichostrongylids (Nematoda: Trichostrongyloidea) of cattle by pellets of Monacrosporium sinense

Avaliou-se a resistência do fungo nematófago Monacrosporium sinense (isolado SF 470) em passar pelo trato gastrintestinal de bovinos e testou-se sua capacidade predatória sobre larvas infectantes de tricostrongilídeos após a passagem. Cem gramas de péletes formulados em matriz de alginato de sódio do isolado fúngico de M. sinense foram administrados, por via oral (VO), a dois bezerros mestiços holandês zebu de seis meses de idade. Para o controle utilizaram-se dois outros animais, de igual padrão, aos quais foram administrados 100g de péletes, VO, livre do isolado fúngico. Amostras fecais, coletadas nos tempos de 12h, 18h, 24h, 48h, 72h e 96h após os tratamentos, foram acondicionadas em placas de Petri e em coproculturas a 25ºC por 15 dias. Houve redução (P<0,05) no número de larvas infectantes de Cooperia spp. e Haemonchus spp. nos animais tratados em relação ao grupo-controle. A diferença ao final do experimento foi de 69,9 por cento nas placas e 61,3 por cento nas coproculturas. O fungo M. sinense demonstrou ser efetivo no controle de larvas infectantes de Cooperia spp e Haemonchus spp em condições de laboratório.

Aplicação de formulação do fungo predador de nematóides Monacrosporium thaumasium (Drechsler, 1937) no controle de nematóides de bovinos / Control of bovine gastrointestinal nematodes using formulation of the nematode-trapping fungus Monacrosporium thaumasium (Drechsler, 1937)

A viabilidade de uma formulação do fungo Monacrosporium thaumasium (Drechsler, 1937) foi avaliada no controle biológico de nematóides parasitos gastrintestinais de bovinos. Dois grupos de sete bezerras cada, mestiças Holandês x Zebu, de quatro a seis meses de idade, foram colocados em pastagens de Cynodon dactilon. No grupo A, cada animal recebeu 20g de pellets (formulação granulada) de M. thaumasium via oral, duas vezes por semana, durante quatro meses, com início na estação chuvosa (outubro, 2001). No grupo B (controle), as bezerras não receberam nenhum tratamento. As contagens de ovos por grama de fezes (OPG) e das larvas infectantes encontradas na pastagem do grupo B foram significativamente maiores (P<0,05) do que as do grupo A e a diferença entre o OPG dos animais dos grupos A e B, no final do experimento, foi de 88,8 por cento. O gênero Cooperia foi o mais prevalente em ambas as pastagens. Conclui-se que a aplicação de pellets de M. thaumasium na dosagem e periodicidade de aplicação usadas foi eficiente no controle de nematóides parasitos gastrintestinais de bovinos.