Electrocardiographic changes in the acute hyperkalaemia produced by intragastric KCl load in rats.

NEW FINDINGS: What is the central question of this study? This study presents a new model for studying the rapid onset of severe, acute hyperkalaemia in rats with intact kidney function by administering an intragastric KCl load. What is the main finding and its importance? This new model of intragastric KCl load produces a reliable and reproducible model for studying the rapid onset of severe, acute hyperkalaemia in rats with intact kidney function. We report unprecedented rapid changes (30 min) in ECG, blood pressure and various arterial blood analyses with this new model, providing a solid foundation for future experiments in this field. ABSTRACT: A variety of animal models have been proposed to study hyperkalaemia, but most of them have meaningful limitations when the goal is to study the effect of potassium overload on healthy kidneys. In this study, we aimed to introduce a new approach for induction of hyperkalaemia in a reliable and reproducible animal model. We used intragastric administration of potassium chloride [KCl 2.3 M, 10 ml/(kg body weight)] to male Holtzman rats (300-350 g) to induce hyperkalaemia. The results showed that this potassium load can temporarily overwhelm the renal and extrarenal handling of this ion, causing an acute and severe hyperkalaemia that can be useful to study the effect of potassium imbalance in a variety of scenarios. Severe hyperkalaemia (>8 meqiv/l) and very profound ECG alterations, characterized by lengthening waves and intervals, were seen as early as 30 min after intragastric administration of KCl in rats. In addition, a transient increase in arterial blood pressure and time-dependent bradycardia were also seen after the KCl administration. No metabolic acidosis was present in the animals, and the potassium ion did not increase proportionally to chloride ion in the blood, leading to an increased anion gap. In conclusion, the results suggest that intragastric KCl loading is a reliable model to promote rapid and severe hyperkalaemia that can be used for further research on this topic.

AV3V lesions reduce the pressor response to L-glutamate into the RVLM.

Neurons from the rostral ventrolateral medulla (RVLM) directly activate sympathetic pre-ganglionic neurons in the spinal cord. Hypertensive responses and sympathetic activation produced by different stimuli are strongly affected by lesions of the preoptic periventricular tissue surrounding the anteroventral third ventricle (AV3V region). Therefore, in the present study, we investigated the effects of acute (1 day) and chronic (15 days) electrolytic lesions of the AV3V region on the pressor responses produced by injections of the excitatory amino acid L-glutamate into the RVLM of unanesthetized rats. Male Holtzman rats with sham or electrolytic AV3V lesions and a stainless steel cannula implanted into the RVLM were used. The pressor responses produced by injections of L-glutamate (1, 5 and 10 nmol/100 nl) into the RVLM were reduced 1 day (9 +/- 4, 39 +/- 6 and 37 +/- 4 mm Hg, respectively) and 15 days after AV3V lesions (13 +/- 6, 39 +/- 4 and 43 +/- 4 mm Hg, respectively, vs. sham lesions: 29 +/- 3, 50 +/- 2 and 58 +/- 3 mm Hg, respectively). Injections of L-glutamate into the RVLM in sham or AV3V-lesioned rats produced no significant change in the heart rate (HR). Baroreflex bradycardia and tachycardia produced by iv phenylephrine or sodium nitroprusside, respectively, and the pressor and bradycardic responses to chemoreflex activation with iv potassium cyanide were not modified by AV3V lesions. The results suggest that signals from the AV3V region are important for sympathetic activation induced by L-glutamate into the RVLM.

Anteroventral third ventricle lesions impair cardiovascular responses to intravenous hypertonic saline infusion.

The anteroventral third ventricle (AV3V) region is a critical area of the forebrain, acting on fluid and electrolyte balance and maintaining cardiovascular homeostasis. The purpose of this study was to determine the effects of lesions to the anteroventral third ventricle region on cardiovascular responses to intravenous hypertonic saline (HS) infusion. Male Wistar rats were anesthetized with urethane. The femoral artery and jugular vein were cannulated to record mean arterial pressure (MAP) and infuse hypertonic saline (3M NaCl, 0.18 mL/100 g bw, over 1 min), respectively. Renal blood flow (RBF) was recorded by ultrasonic transit-time flow probes. Renal vascular conductance (RVC) was calculated as renal blood flow to mean arterial pressure ratio and expressed as percentage of baseline. After hypertonic saline infusion in sham animals, renal blood flow and renal vascular conductance increased to 137+10% and 125+7% (10 min), and 141+/-10% and 133+/-10% (60 min), respectively. Increases in mean arterial pressure (20-min peak: 12+/-3 mm Hg) were also observed. An acute lesion in the AV3V region (DC, 2 mA 25s) 30 min before infusion abrogated the effects of hypertonic saline. Mean arterial pressure was unchanged and renal blood flow and renal vascular conductance were 107+/-7% and 103+/-6% (10 min), and 107+/-4 and 106+/-4% (60 min), respectively. Marked tachycardia was observed immediately after lesion. Responses of chronic sham or lesioned rats were similar to those of acute animals. However, in chronic lesioned rats, hypertonic saline induced sustained hypertension. These results demonstrate that integrity of the AV3V region is essential for the renal vasodilation that follows acute changes in extracellular fluid compartment composition.

Vias e mecanismos neurais envolvidos nos ajustes cardiovasculares induzidos pela expansäo de volume em ratos / Pathways and mechanisms involved neural in cardiovascular measured induzed by volume expansion in anaesthetized rats

A manutenção do volume e da composição do líquido extracelular (LEC) dentre de limites estreitos é essencial para a homeostasia celular. Variações no volume do LEC e de sua composição são rapidamente detectados pelo sistema nervoso central (SNC) através de sinais provenientes dos osmorreceptores centrais e periféricos, concentração plasmática de hormônios circulantes, e pelos barorreceptores e receptores cardiopulmonares. A expansão aguda do volume circulante produz respostas neurais, renais, cardiovasculares e hormonais, que tem como objetivo aumentar a diurese e natriurese até que os níveis basais do LEC sejam restabelecidos. Neste estudo, nos propusemos a determinar: 1. as vias aderentes envolvidas nas respostas cardiovasculares à expansão de volume (EV); 2. as vias centrais e os mecanismos envolvidos nestas respostas. Ratos Wistar machos (280-320 g) foram anestesiados com uretana iv (1.2 g/kg, iv) após indução com halotana (2 por cento em 1OO por cento de 02). Catéteres foram inseridos em ambas veias femorais e na artéria femoral esquerda para administração de drogas, VE e medidas de pressão arterial média (MAP), respectivamente. Sondas foram posicionadas ao redor da artéria renal esquerda e da aorta abdominal inferior para o registro do fluxo sanguíneo renal (FR) e dos membros posteriores (FMP), respectivamente. O FR e o FMP foram medidos por fluxometria Doppler e expresso como percentagem do basal. A condutância vascular relativa (CR e CMP) foi calculada com a razão variação Doppler e MAP e expressas como percentagem do basal. A EV foi realizada pela infusão de Ficoll 4 por cento (Pharmacia), 1 por cento do peso corporal a O,4 mL/min. MAP, freqüência cardíaca (FC), e os fluxos renal e dos membros posteriores e as condutâncias vasculares foram registradas por 60 min após o início da EV. Os resultados obtidos demonstraram que: a. em animais controles, a EV produziu um aumento transitório (< 20 min) na PAM e vasodilatação mantida (ü 60 min) nos leitos renal e dos membros posteriores; b. após a vagotomia bilateral (remoção dos receptores cardiopulmonares), os ajustes cardiovasculares induzidos pela EV foram semelhantes aos dos animais controles; c. em ratos com desnervação sino-aórtica (remoção dos barorreceptores arteriais) a resposta pressora da EV estava aumentada, mas a vasodilatação renal foi bloqueada, enquanto que a vasodilatação dos membros posteriores foi semelhante ao obsrevada em ratos controle; d. em ratos com denesvação ...(au)