Renal effects of angiotensin II receptor subtype 1 and 2-selective ligands injected into the paraventricular nucleus of conscious rats

We determined the effects of losartan and CGP42112A (selective ligands of the AT1 and AT2 angiotensin receptors, respectively) and salarasin (a relatively nonselective angiotensin receptor antagonist) on urinary volume and urinary sodium and potassium excretion induced by administration of angiotensin II (ANG II) into the paraventricular nucleus (PVN) of conscious rats. Both the AT1 and AT2 ligands and salarasin administered in the presence of ANG II elicited a concentration-dependent inhibition of urine excretion, but losartan inhibited only 75% of this response. The IC50 for salarasin, CGP42112A, and losartan was 0.01, 0.05, and 6 nM, respectively. Previous treatment with saralasin, CGP42112A and losartan competitively antagonized the natriuretic responses to PVN administration of ANG II, and the IC50 values were 0.09, 0.48, and 10 nM, respectively. The maximum response to losartan was 65% of that obtained with saralasin. Pretreatment with saralasin, losartan, and CGP42112A injected into the PVN caused shifts to the right of the concentration-response curves, but the losartan concentrations were disproportionately greater compared with salarasin or CGP42112A. The IC50 values were 0.06, 0.5, and 7.0 for salarasin, CGP42112A, and losartan, respectively. These results suggest that both AT1 and AT2 receptor subtypes in the PVN are involved in ANG II-related urine, sodium, and potassium excretion, and that the inhibitory responses to AT2 blockade are predominant. Copyright (C) 1999 Elsevier Science B.V.

Efeito do extrato aquoso de sete-sangrias [Cuphea mesostemon (Koehne) Lourt] sobre o fluxo de água, medido em bexiga urinária de sapo in vitro

The Cuphea mesostemon specie, known as sete-sangrias, is widely used as a diuretic substance in popular medicine. As the toad urinary bladder is an epithelium analogous to the distal nephron of mammals, it is used in order to study the transport water and electrolytes in many laboratories. This preparation permits excellent observation in water flow, from the urinary bladder lumen to the external side or the serosal one (water re-absorption), by means of gravimetrical measures. In the present work the hydrosmotic effect of aqueous extract (AE) of sete-sangrias leaf was studied. A 20% solution was added to the serosal side (S) of the bladder preparation, and the water flow was measured every 15 minutes after that. The results showed that 4mL of AE in the S side, increased the JH20 in a significant manner (p<0,05). This effect had a dose - response shape, with the volumes of 0,2mL, 0,4mL and 0,8mL of AE in the S bath. The hydro-osmotic effect of the anti-diuretic hormone (ADH) was studied as well and a significant stimulation (p<0,05) in the JH2O was observed with the magnitude of 150%. The AE effect was similar to the ADH one, and was not antagonized by this hormone. We concluded that Cuphea possesses an anti-diuretic activity similar to that presented by ADH, in toad urinary bladder, in vitro.

Influence of angiotensin II receptor subtypes of the paraventricular nucleus on the physiological responses induced by angiotensin II injection into the medial septal area

Objective - We determined the effects of losartan and PD 123319 (antagonists of the AT1 and AT2 angiotensin receptors, respectively), and [Sar1, Ala8] ANG II (a relatively peptide antagonist of angiotensin receptors) injected into the paraventricular nucleus (PVN) on water and 3% NaCl intake, and the diuretic, natriuretic, and pressor effects induced by administration of angiotensin II (ANG II) into the medial septal area (MSA) of conscious rats. Methods - Holtzman rats were used. Animals were anesthetized with tribromoethanol (20 mg) per 100 grams of body weight, ip. A stainless steel guide cannula was implanted into the MSA and PVN. All drugs were injected in 0.5-μl volumes for 10-15 seconds. Seven days after brain surgery, water and 3% NaCl intake, urine and sodium excretion, and arterial blood pressure were measured. Results - Losartan (40 nmol) and [Sar1, Ala8] ANG II (40 nmol) completely eliminated whereas PD 123319 (40 nmol) partially blocked the increase in water and sodium intake and the increase in arterial blood pressure induced by ANG II (10 nmol) injected into the MSA. The PVN administration of PD 123319 and [Sar1, Ala8] ANG II blocked whereas losartan attenuated the diuresis and natriuresis induced by MSA administration of ANG II. Conclusion - MSA involvement with PVN on water and sodium homeostasis and arterial pressure modulation utilizing ANGII receptors is suggested.

The comparative efficacy of yohimbine and atipamezole to treat amitraz intoxication in dogs

This study compared the efficacy of yohimbine with atipamezole, a new α2-adrenergic antagonist, to treat canine amitraz intoxication. Thirty dogs were divided equally into 3 groups (A, AY, and AA). Group A received 2.5% amitraz iv at 1 mg/kg; Group AY received the same dose of amitraz followed 30 min later by 0.1 mg/kg (2 mg/mL) yohimbine iv; and Group AA received the same dose of amitraz followed 30 min later by 0.2 mg/kg (5 mg/mL) atipamezole iv. Temperature, heart rate, respiratory frequency, mean arterial pressure, degree of sedation, mean time of tranquilization and diameter of pupils were monitored for 360 min. Sedation, logs of reflexes, hypothermia bradycardia, hypotension, bradypnea and mydriasis were observed in Group A, with 3rd eyelid prolapse, increased diuresis and vomiting in some animals. Yohimbine reversed all alterations induced by amitraz, but induced significant cardiorespiratory effects such as tachycardia and tachypnea. Atipamezole was a useful antagonist for amitraz, with less cardiorespiratory effects, suggesting its potential role as an alternative treatment of amitraz intoxication in dogs.

Efeitos hipotensivo e diurético dos extratos aquosos de pitanga (Eugenia uniflora L.) e jambolão (Eugenia jambolana Lam.) em ratos normotensos anestesiados

Plants that possess a diuretic effect are widely used by people in the treatment of some important diseases as edema and hypertension. The objective of this work was to study the effects of pitanga and jambos aqueous extracts (AE) about the arterial pressure (AP) and urinary flow (V) in normotensive and anesthetized rats. The AE were prepared for the decoction method and administrated for intragastric way in different concentrations: 10%, 15%, 20% and 25%. These concentrations corresponded respectively at doses of 56, 94, 145, 172 mg of pitanga dried extract /Kg and 44, 73, 83, 95 mg of jambos dried extract/Kg. The animals were divided in nine groups with seven individuals (n=7): control (C), P-10%, P-15%, P-20%, P-25%, J-10%, J-15%, J-20% and J-25%. The rats were anesthetized (hypnol 3%) and submitted to tracheotomy. The left carotide artery was catheterized to measure the AP through a mercury manometer, in periods of 15 minutes. The bladder was catheterized for urine collection and to measure the V, in periods of 30 minutes. The experimental protocol was divided in four periods of 30 minutes each: basal (to evaluate of the basal parameters) and experimental (Exp) 1, 2 and 3 (after the administration of the AE). The results were analyzed for ANOVA and Tukey (X±SD, p<0.05). In the C group did have not alteration of the AP basal but the V basal increased. In the experimental groups (AE of P and J) had significative decline in the AP basal: 34% (P-10%), 20% (P-15%), 21% (P-20%), 31% (P-25%), 24% (J-10%), 20% (J-15%) 16% (J-20%) and 29% (J-25%). Moreover, the administration of AE increased the V basal in: 280% (P-15%) and 192% (J-20%). The results showed that the plants evaluated are hypotensive and diuretic.

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.

The number of podocyte and slit diaphragm is decreased in experimental diabetic nephropathy

Purpose: To determine the number of podocyte, slit diaphragms, slit diaphragm extensions and GBM thickness in diabetic nephropathy. Methods: Sixty Rattus Wistarof both sexes weighing 200-300g were divided in two experimental groups: normal group 10 animals, and alloxan diabetic rats - 50 animals. Alloxan was administered in a single IV dose of 42mg/kg body weight. Body weight, water and food intake, diuresis, and blood and urine glucose were determined in both groups before alloxan injection and two weeks, six and twelve months after alloxan injection. Proteinuria was measured at 12 months in both groups. After 12 months animals were sacrificed, and the right kidney processed for electron microscopy. Results: Clear clinical and laboratory signs of severe diabetes were seen, in all alloxan-diabetic rats at all follow-up times. Glomerular basement membrane (GBM) thickening, podocyte number, and slit diaphragm number and extension were determined. GBM of all diabetic rats was significantly thicker (median=0.29μm; semi-interquartile range=0.065μm) than in the normal rats (0.23μm; 0.035μm). Diabetic rat podocyte number (8; 1), slit diaphragm number (4; 1), and slit diaphragm extension (0.021μm; 0.00435μm) were significantly lower than in normal rats (11; 1) and (7; 1.5), and (0.031μm; 0.0058μm). Diabetic rat proteinuria (0.060mg/24h; 0.037mg/24h) was higher than in normal rats (0.00185mg/24h; 0.00055mg/24h). Conclusion: Experimental diabetes is associated with significant (p<0.05) changes in podocyte foot process, slit number, slit diaphragm extension, and GBM thickness.

Hypothyroidism and acute kidney injury: An unusual association

Association between severe hypothyroidism and acute kidney injury (AKI) is rare. A 40-year-old woman presented with 15 days history of generalised muscle pain, weakness, weight gain and oedema. Medical history: hypertension and hypothyroidism. Physical examination: dry skin, peripheral/periorbital oedema, slow thought and speaking, thyroid increased. Laboratory examinations: high levels of creatine kinase , creatinine, uric acid and lactate dehydrogenase. Free T4 was very low (<0.3 ng/dL) and thyroid-stimulating hormone was high (21.7 mIU/mL). Urinalysis showed haem pigment without haematuria. We performed the diagnosis of AKI secondary to hypothyroidism-induced rhabdomyolysis. Intravenous fluids were started, urinary alkalisation and increased l-thyroxine dose replacement. On the day after admission, forced diuresis with furosemide was introduced leading to a progressive improvement of symptoms. Although hypothyroidism and AKI is unusual, it should be suspected in patients presenting decrease of renal function and high creatine kinase in the absence of other causes of rhabdomyolysis.

Estudo das alterações estruturais e ultra-estruturais da camada de fotorreceptores da retina de ratos diabéticos aloxânicos

Pós-graduação em Bases Gerais da Cirurgia - FMB

Avaliação da formação óssea em implantes dentários de ratos não diabéticos, diabéticos não controlados e controlados com insulina

Pós-graduação em Bases Gerais da Cirurgia - FMB

Avaliação ultra-estrutural do endotélio corneal de ratos normais e de diabéticos aloxânicos

Pós-graduação em Bases Gerais da Cirurgia - FMB

Avaliação seminal e testicular de cães submetidos à administração de cisplatina

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

Efeitos renais e sobre a concentração do hormônio antidiurético pelo uso de dexmedetomidina em cães anestesiados e submetidos à isquemia renal

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Alterações testiculaes no diabetes aloxânico no rato: estudo morfométrico e ultraestrutural dos túbulos seminíferos

Pós-graduação em Bases Gerais da Cirurgia - FMB

Avaliação ultra-estrutural dos vasos da íris, corpo ciliar e retina em ratos diabéticos aloxânicos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)