Cross-talk with β2-adrenoceptors enhances ligand affinity properties from endothelial alpha1D-adrenoceptors that mediates carotid relaxation

Objectives Our main objectives were to investigate the affinity properties of endothelial and muscular α1D-adrenoceptors and to characterize the cross-talk between endothelial α1D- adrenoceptors and β2-adrenoceptors in rat carotid. Methods Relaxation and contraction concentration-response curves for phenylephrine (α1-adrenergic agonist) were obtained in carotid rings in absence or presence of increasing concentrations of BMY7378 (α 1D-adrenergic antagonist), combined or not with increasing concentration of ICI-118,551 (β2-adrenergic antagonist). Schild analysis was used to estimate the affinity constant from pA2 values of BMY7378. Key Findings BMY7378 produced an unsurmountable antagonism on phenylephrine-induced relaxation but a surmountable antagonism on phenylephrine-induced contraction. BMY7378 potency was higher in inhibiting the relaxation than the contraction induced by phenylephrine because the rightward shifts induced by BMY7378 were greater in the relaxation. The apparent pA 2 value for BMY7378 in phenylephrine-induced relaxation was greater than in contraction. When combined with ICI-118,551, BMY7378 yielded a surmountable antagonism on phenylephrine-induced relaxation and presented a pA2 value similar to that obtained in phenylephrine-induced contraction. Conclusions Endothelial α1D-adrenoceptors, which mediates rat carotid relaxation, present high ligand affinity because of the cross-talk with β2-adrenoceptors, which explains the higher potency of phenylephrine in inducing relaxation than contraction and the atypical unsurmountable antagonism produced by BMY7378 on phenylephrine-induced relaxation. © 2013 Royal Pharmaceutical Society.

Systemic blood flow relations in conscious South American rattlesnakes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Time course of training-induced microcirculatory changes and of vegf expression in skeletal muscles of spontaneously hypertensive female rats

Exercise-induced vessel changes modulate arterial pressure (AP) in male spontaneously hypertensive rats (SHR). Vascular endothelial growth factor (VEGF) is important for angiogenesis of skeletal muscle. The present study evaluated the time course of VEGF and angiogenesis after short- and long-term exercise training of female SHR and Wistar Kyoto (WKY) rats, 8-9 weeks (200-250 g). Rats were allocated to daily training or remained sedentary for 3 days (N = 23) or 13 weeks (N = 23). After training, the carotid artery was catheterized for AP measurements. Locomotor (tibialis anterior and gracilis) and non-locomotor skeletal muscles (temporalis) were harvested and prepared for histologic and protein expression analyses. Training increased treadmill performance by all groups (SHR = 28%, WKY = 64%, 3 days) and (SHR = 141%, WKY = 122%, 13 weeks). SHR had higher values of AP than WKY (174 ± 4 vs 111 ± 2 mmHg) that were not altered by training. Three days of running increased VEGF expression (SHR = 28%, WKY = 36%) simultaneously with an increase in capillary-to-fiber ratio in gracilis muscle (SHR = 19%, WKY = 15%). In contrast, 13 weeks of training increased gracilis capillary-to-fiber ratio (SHR = 18%, WKY = 19%), without simultaneous changes in VEGF expression. Training did not change VEGF expression and capillarity of temporalis muscle. We conclude that training stimulates time- and tissue-dependent VEGF protein expression, independent of pressure levels. VEGF triggers angiogenesis in locomotor skeletal muscle shortly after the exercise starts, but is not involved in the maintenance of capillarity after long-term exercise in female rats.

Prevention of renal ischemia/reperfusion injury in rats using acetylcysteine after anesthesia with isoflurane

OBJETIVO: Avaliar o efeito da N-acetilcisteína na proteção renal contra lesão de isquemia/reperfusão, quando administrada logo após a indução anestésica, em ratos anestesiados com isoflurano. MÉTODOS: Dezoito ratos Wistar machos pesando mais que 300g foram anestesiados com isoflurano. A jugular interna direita e a carótida esquerda foram dissecadas e canuladas. Os animais foram distribuídos aleatoriamente em GAcetil, recebendo N-acetilcisteína por via intravenosa, 300mg/kg, e GIsot, solução salina. Foi realizada nefrectomia direita e clampeamento da artéria renal esquerda por 45 min. Os animais foram sacrificados após 48h, sendo colhidas amostras sanguíneas após a indução anestésica e ao sacrifício dos mesmos para avaliar a creatinina sérica. Realizou-se histologia renal. RESULTADOS: A variação da creatinina foi 2,33mg/dL ± 2,21 no GAcetil e 4,38mg/dL ± 2,13 no GIsot (p=0,074). Dois animais apresentaram necrose tubular intensa no GAcetil, comparados a cinco no GIsot. Apenas GAcetil apresentou animais livres de necrose tubular (dois) e degeneração tubular (um). CONCLUSÃO: Após isquemia/reperfusão renais, os ratos aos quais se administrou N-acetilcisteína apresentaram menor variação na creatinina sérica e lesões renais mais leves que o grupo controle.

Aneurisma cerebral e cisto de aracnóide: a propósito de caso com hemorragia intracística

Relatamos um caso de aneurisma da bifurcação da artéria carótida interna, cuja ruptura se deu para dentro de cisto de aracnóide da fissura silviana. em revisão da literatura apenas 3 casos foram descritos. Discutimos ainda os aspectos clínicos atípicos do caso, as características dos achados cirúrgicos e uma correlação etiopatogênica entre as duas patologias.

Caroticoclinoid foramen in human skulls: incidence, morphometry and its clinical implications

The caroticoclinoid foramen is an inconstant structure, formed by the union of the anterior and middle clinoid processes. The aim of this study was to perform an incidence and morphometry of the caroticoclinoid foramen in Brazilian human skulls and discuss its clinical implications. Eighty dry human skulls with sex distinction were used, and 3 groups of incidence were determined: General, sex, and sides. The morphometry was performed using a manual caliper and the major diameter of the foramina was measured; the values were also divided in general, according to sex and sides. The incidence of skulls with at least one foramen was 8.5%. According to the sides, 8.5% of the skulls showed foramen on the right side and 2.5% on the left. We found 2.5% of the skulls with bilateral foramen and 6.25% with unilateral foramen. In relation to sex, the foramens were found in 5% of male skulls and 12.5% of female skulls. The major diameter of this structure presented on mean, values of 5.23 mm on general, 5.18 mm on the right side and 5.35 mm on the left, 5.30 mm in male skulls and 5.18 mm in female skulls. The anatomical characteristics of this foramen should be considered in view of its clinical implications associated with neurosurgery as clinoid process removal, and symptoms as headache due to internal carotid artery alterations in this region. In conclusion knowledge of this structure supports the diagnosis and treatment of clinical complications related to this variation.

Efeito do extrato aquoso de cabelo de milho (Zea mays L.) sobre a excreção renal de água e eletrólitos e pressão arterial em ratos Wistar anestesiados

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Avaliação de dois modelos experimentais de isquemia e reperfusão cerebral em ratos com oclusão temporária carotídea associada ou não à oclusão vertebral

OBJETIVO: Avaliar a reprodutibilidade de dois modelos experimentais de isquemia e reperfusão cerebral. MÉTODOS: 60 ratos foram distribuídos, aleatoriamente, em três grupos experimentais, com 20 animais cada: I - pinçamento temporário de artéria carótida esquerda; II - cauterização prévia das artérias vertebrais e pinçamento temporário da artéria carótida esquerda; simulado - sem isquemia nem reperfusão. Todos os animais tiveram oclusão definitiva de artéria carótida direita e os três grupos foram subdivididos em dois períodos de reperfusão: A - 60 minutos e B - 120 minutos. Os parâmetros verificados foram: medidas de pressão arterial média sistêmica e fluxo sangüíneo carotídeo; medida de malondialdeído cerebral através do teste TBARS e avaliação histológica do hemisfério cerebral submetido à isquemia e reperfusão. Foi feito também um estudo complementar com angiografia cerebral em 5 animais adicionais. RESULTADOS: Não houve diferenças significativas nas dosagens de malondialdeído cerebral e na freqüência e gravidade das alterações histológicas cerebrais entre os três grupos. Nos grupos GI e GII, a PAM foi significantemente maior no período de isquemia. O fluxo sangüíneo entre os períodos pré e pós-pinçamento aumentou nos grupos IA e IIB, diminuiu no grupo IB e no grupo IIA manteve-se inalterado. As angiografias do estudo complementar mostraram aporte sangüíneo para cérebro através de circulação colateral. CONCLUSÃO: Os modelos de isquemia e reperfusão estudados não demonstraram alterações consistentes de marcadores de lesão cerebral, seja quanto à produção de lipoperóxidos ou de lesões histológicas.

Granulocyte colony-stimulating factor expression from transduced vascular smooth muscle cells provides sustained neutrophil increases in rats

Granulocyte colony-stimulating factor (G-CSF) regulates granulocyte precursor cell proliferation, neutrophil survival, and activation. Cyclic hematopoiesis, a disease that occurs both in humans and grey collie dogs is characterized by cyclical variations in blood neutrophils. Although the underlying molecular defect is not known, long-term daily administration of recombinant G-CSF eliminates the severe recurrent neutropenia, indicating that expression of G-CSF by gene therapy would be beneficial. As a prelude to preclinical studies in affected collie dogs, we monitored hematopoiesis in rats receiving vascular smooth muscle cells transduced to express G-CSF. Cells transduced with LrGSN, a retrovirus expressing rat G-CSF, were implanted in the carotid artery and control animals received cells transduced with LASN, a retrovirus expressing human adenosine deaminase (ADA). Test animals showed significant increases in neutrophil counts for at least 7 weeks, with mean values of 3,670 +/- 740 cells/mu l in comparison to 1,870 +/- 460 cells/mu l in controls (p < 0.001). Thus, in rats G-CSF gene transfer targeted at vascular smooth muscle cells initiated sustained production of 1,800 neutrophils/mu l, a cell number that would provide clinical benefit to patients. Lymphocytes, red cells and platelets were not different between control and test animals (p > 0.05). These studies indicate that retrovirally transduced vascular smooth muscle cells can provide sustained clinically useful levels of neutrophils in vivo.

Effect of passive pneumoperitoneum on oesophageal pressure, cardiovascular parameters and blood gas analysis in horses

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

About the arterial blood vessels pelvic opossum's (Didelphis albiventris) behaviour

The work consists of the study of 20 opossums (Didelphis albiventris); 7 females and 13 males, adults, natives of Jaboticabal county proceeding to a canulation and injection of the arterial system with neoprene latex-650 in the aorta artery (full-blooded). Right away the preparations were fixed by a 10% formaldehyde aqueous solution and afterwards dissected and formed a scheme. The analysis of the pieces showed that in the opossum, the end of the aorta always divides in the common iliac artery, right and left sides, both originating the external and internal iliac artery, on the right and left sides. The medium sacral artery results, medianly, from the aorta division's angle in 2 common iliac arteries in 8 cases (40% - 6 males and 2 females); this vessel comes from the left common iliac artery in 7 animals (35% - 5 males and 2 females) or comes from the right common iliac artery, in 5 preparations (25% - 3 females and 2 males). The deep iliac circumflex artery is born by the common iliac artery from the right side in 10 preparations (50% - 6 males and 4 females), can appear as well, concomitantly with the external and internal iliac artery, from the right side in 9 pieces (45% - 6 males and 3 females) and further from the right this vessels can emerge from the external iliac artery, in 1 case only (5% - 1 male).

Efeitos do extrato aquoso de cebola (Allium cepa L.) sobre a função renal e a pressão arterial em ratos Wistar

The vegetal species, Allium cepa, known as onion, is widely used in the folk medicine as diuretic, besides it has been used on the bronchitis, cough, cardiovascular diseases and hypertension treatment. In this study we evaluate the onion aqueous extract (AE) effect on water flow and electrolytes in anesthetized Wistar rats, besides we also evaluate arterial pressure alterations. Two groups were studied: Group 1 (control) - oral tratment with 1.0 mL of distilled water, and Group 2 (experimental) - oral treatment with 1.0 mL of AE 20%. The rats were anesthetized and we canulate the trachea, left carotide artery (for arterial pressure measurement and blood collecting), jugular vein (to execute inulin perfusion - to register glomerular filtration), and urinary bladder (to collect urine). The Group 1 results had shown that the animals had not presented significant alterations (p>0.05) in the analyzed parameters. The animals of Group 2 had a significant reduction (p<0.05) in the arterial pressure (22.0%). However, there were not significant alterations in renal parameters (p>0.05). These results show that the treatment with the AE lead a hypotensor effect in anesthetized Wistar rats, but not followed by renal parameters alterations.

Treatment of atherosclerotic renovascular disease

Treatment of atherosclerotic renovascular disease is controversial and revascularization is not a beneficial approach to all patients. Conditions as progressive deterioration of renal function, refractory hypertension or accelerated cardiovascular disease, especially recurrent pulmonary edema, could profit from renal angioplasty with stent placement. Surgical revascularization is a good option for patients who will need concomitant surgical corrections of abdominal aortic lesions. Treatment of all other patients must be individualized. Medical therapy is indicated for all patients with atherosclerotic renovascular disease. Observational studies pointed out to the beneficial effect of controlling blood pressure (<130/80 mm Hg), glucose and lipids profile, lifestyle modifications, specific use of platelet antiaggregant therapy, Angiotensin Conversion Enzyme Inhibitors (ACEI) and statins. All others cardiovascular risk factors must be controlled. The evaluation and management of other systemic atherosclerotic vascular lesions is important, especially coronary, carotid and abdominal aortic. This paper presents a review of evidences to rationale the atherosclerotic renovascular disease treatment. © 2008 Bentham Science Publishers Ltd.

Efeito hipotensor do extrato aquoso de alpiste (Phalaris canariensis L.) em ratos

The plant species Phalaris canariensis, known as canary grass, is widely used in folk medicine as diuretic, as well as in culinary and animal feed. In this study, the effect of P. canariensis aqueous extract (AE) on water flow (V) and sodium renal excretion (Qe (Na+)) was evaluated in anesthetized Wistar rats. Arterial pressure alterations (AP) were also assessed. Two groups were studied: Control group (CON) - oral administration of 1.0 mL distilled water, and Experimental group (EA) - oral administration of 1.0 mL P. canariensis aqueous extract 40%. Rats were anesthetized and subjected to cannulation of trachea (for better pulmonary ventilation), left carotid artery (for arterial pressure measurement) and urinary bladder (for urine collection). Control animals did not present significant alterations (p>0.05) in all analyzed parameters after water administration. EA group had a significant arterial pressure reduction at 60 minutes (31.4%) and 90 minutes (49.1%) after the extract administration (p<0.05). Renal parameters did not have any significant alteration (p>0.05). In this study, P. canariensis aqueous extract had a hypotensive effect in anesthetized Wistar rats, without renal alterations.

Proteção renal com eritropoetina em modelo de isquemia renal no rato

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)