A low concentration of ouabain (0.18 µg/kg) enhances hypertension in spontaneously hypertensive rats by inhibiting the Na+ pump and activating the renin-angiotensin system

We investigated the effects of low ouabain concentrations on systolic (SAP) and diastolic (DAP) arterial pressures and on pressor reactivity in 3-month-old male spontaneously hypertensive rats (SHR). Arterial blood pressure (BP) and pressor reactivity to phenylephrine (PHE) were investigated before and after 0.18 μg/kg ouabain administration (N = 6). The influence of hexamethonium (N = 6), canrenone (N = 6), enalapril (N = 6), and losartan (N = 6) on ouabain actions was evaluated. Ouabain increased BP (SAP: 137 ± 5.1 to 150 ± 4.7; DAP: 93.7 ± 7.7 to 116 ± 3.5 mmHg; P < 0.05) but did not change PHE pressor reactivity. Hexamethonium reduced basal BP in control but not in ouabain-treated rats. However, hexamethonium + ouabain increased DAP sensitivity to PHE. Canrenone did not affect basal BP but blocked ouabain effects on SAP. However, after canrenone + ouabain administration, DAP pressor reactivity to PHE still increased. Enalapril and losartan reduced BP and abolished SAP and DAP responses to ouabain. Enalapril + ouabain reduced DAP reactivity to PHE, while losartan + ouabain reduced SAP and DAP reactivity to PHE. In conclusion, a small dose of ouabain administered to SHR increased BP without altering PHE pressor reactivity. Although the renin-angiotensin system (RAS), Na+ pump and autonomic reflexes are involved in the effects of ouabain on PHE reactivity, central mechanisms might blunt the actions of ouabain on PHE pressor reactivity. The effect of ouabain on SAP seems to depend on the inhibition of both Na+ pump and RAS, whereas the effect on DAP seems to depend only on RAS.

Effects of small doses of ouabain on the arterial blood pressure of anesthetized hypertensive and normotensive rats

Ouabain increases vascular resistance and may induce hypertension by inhibiting the Na+ pump. The effects of 0.18 and 18 µg/kg, and 1.8 mg/kg ouabain pretreatment on the phenylephrine (PHE; 0.1, 0.25 and 0.5 µg, in bolus)-evoked pressor responses were investigated using anesthetized normotensive (control and uninephrectomized) and hypertensive (1K1C and DOCA-salt treated) rats. Treatment with 18 µg/kg ouabain increased systolic and diastolic blood pressure in all groups studied. However, the magnitude of this increase was larger for the hypertensive 1K1C and DOCA-salt rats than for normotensive animals, while the pressor effect of 0.18 µg/kg ouabain was greater only in DOCA-salt rats. A very large dose (1.8 mg/kg) produced toxic effects on the normotensive control but not on uninephrectomized or 1K1C rats. Rat tail vascular beds were perfused to analyze the effects of 10 nM ouabain on the pressor response to PHE. In all animals, 10 nM ouabain increased the PHE pressor response, but this increase was larger in hypertensive DOCA-salt rats than in normotensive and 1K1C rats. Results suggested that a) increases in diastolic blood pressure induced by 18 µg/kg ouabain were larger in hypertensive than normotensive rats; b) in DOCA-salt rats, smaller ouabain doses had a stronger effect than in other groups; c) hypertensive and uninephrectomized rats were less sensitive to toxic doses of ouabain, and d) after treatment with 10 nM ouabain isolated tail vascular beds from DOCA-salt rats were more sensitive to the pressor effect of PHE than those from normotensive and 1K1C hypertensive rats. These data suggest that very small doses of ouabain, which might produce nanomolar plasma concentrations, enhance pressor reactivity in DOCA-salt hypertensive rats, supporting the idea that endogenous ouabain may contribute to the increase and maintenance of vascular tone in hypertension.

Effects of ouabain on vascular reactivity

Ouabain is an endogenous substance occurring in the plasma in the nanomolar range, that has been proposed to increase vascular resistance and induce hypertension. This substance acts on the a-subunit of Na+,K+-ATPase inhibiting the Na+-pump activity. In the vascular smooth muscle this effect leads to intracellular Na+ accumulation that reduces the activity of the Na+/Ca2+ exchanger and to an increased vascular tone. It was also suggested that circulating ouabain, even in the nanomolar range, sensitizes the vascular smooth muscle to vasopressor substances. We tested the latter hypothesis by studying the effects of ouabain in the micromolar and nanomolar range on phenylephrine (PE)-evoked pressor responses. The experiments were performed in normotensive and hypertensive rats in vivo, under anesthesia, and in perfused rat tail vascular beds. The results showed that ouabain pretreatment increased the vasopressor responses to PE in vitro and in vivo. This sensitization after ouabain treatment was also observed in hypertensive animals which presented an enhanced vasopressor response to PE in comparison to normotensive animals. It is suggested that ouabain at nanomolar concentrations can sensitize vascular smooth muscle to vasopressor stimuli possibly contributing to increased tone in hypertension.

Determinação do momento crítico de flambagem lateral com distorção em vigas mistas contínuas de aço e concreto com perfis de alma senoidal

As vigas mistas de aço e concreto estão sendo largamente utilizadas em construções de edifícios e pontes. Ao se combinar o aço com o concreto obtêm-se estruturas mais econômicas, uma vez que se tira proveito das melhores características de cada material. Nas regiões de momento negativo de uma viga mista contínua, a mesa inferior e parte da alma estão comprimidas, se a alma do perfil não tiver rigidez suficiente para evitar a flexão lateral, ela distorcerá gerando um deslocamento lateral e um giro na mesa comprimida, caracterizando um modo de flambagem denominado flambagem lateral com distorção (FLD). O procedimento de verificação à FLD da EN 1994-1-1:2004 originou o método de cálculo da ABNT NBR 8800:2008, entretanto a EN 1994-1-1:2004 não fornece expressão para o cálculo do momento crítico elástico, enquanto a ABNT NBR 8800:2008 prescreve uma formulação proposta por Roik, Hanswille e Kina (1990) desenvolvida para vigas mistas com perfis de alma plana. Embora as normas prescrevam um método de verificação à FLD para vigas mistas com perfis de alma plana, poucos estudos têm sido feitos sobre esse estado-limite. Além disso, tanto a ABNT NBR 8800:2008 quanto as normas internacionais não abordam perfis de alma senoidal. Neste trabalho, foram implementadas análises de flambagem elástica, com auxílio do software ANSYS 14.0 (2011), em modelos de elementos finitos que retratem o comportamento à FLD de vigas mistas de aço e concreto com perfis de alma plana e senoidal. Os modelos numéricos foram constituídos pelo perfil de aço, por uma mola rotacional que restringe parcialmente o giro da mesa superior e uma restrição ao deslocamento lateral, ao longo de todo o comprimento da viga. Os resultados numéricos são comparados com os obtidos pelas formulações de Roik, Hanswille e Kina (1990) e de Hanswille (2002), adaptadas para levar em consideração a corrugação da alma do perfil de aço. Para avaliação das formulações supracitadas e da consistência da modelagem numérica adotada, o momento crítico elástico foi determinado para vigas mistas com perfis de aço de alma plana. Como resultado, um método para o cálculo do momento crítico elástico de vigas mistas de alma senoidal é proposto.