Role of kinins in the control of renal papillary blood flow, pressure natriuresis, and arterial pressure.

The present study evaluated the effects of blocking kinins with the bradykinin B(2) receptor antagonist Hoe140 on the relationship between renal perfusion pressure, papillary blood flow (PBF), and sodium excretion. To determine the relevance of renal kinins in the long-term control of arterial pressure, the effect of a chronic intrarenal infusion of Hoe140 on arterial pressure and sodium balance was also studied. PBF was not autoregulated in volume-expanded rats, and the administration of Hoe140 reduced PBF (-30%) and improved PBF autoregulation. The kinin antagonist also decreased sodium excretion (-35%) and blunted pressure natriuresis with no whole-kidney renal hemodynamic changes. These effects may be mediated through nitric oxide (NO), because in rats pretreated with N(G)-nitro-L-arginine methyl ester, Hoe140 had no additional effects on PBF or pressure natriuresis. A role for NO in mediating the renal response to Hoe140 is also supported by the finding that Hoe140 reduced basal urinary NO(3)(-)/NO(2)(-) excretion (-33%), and it blunted the arterial pressure-induced increase in NO(3)(-)/NO(2)(-) excretion, which is compatible with the idea that the pressure-natriuresis response may be mediated through kinins and NO. The importance of kinins in long-term regulation of arterial pressure is demonstrated by the severe arterial hypertension (172+/-6 mm Hg) induced during the chronic intrarenal infusion of Hoe140 associated with sodium and volume retention. These data suggest that renal kinins and NO may be a part of the renal mechanism coupling changes in arterial pressure with modifications in PBF and sodium excretion, therefore contributing to the long-term control of arterial pressure.

Interactions between nitric oxide and renal nerves on pressure-diuresis and natriuresis.

The present study examined the effect of renal denervation on the impairment of the pressure-diuresis response produced by nitric oxide synthesis blockade. The experiments were performed in Inactin-anesthetized Munich-Wistar rats. The animals with innervated kidneys had lower baseline values of renal blood flow, GFR, sodium excretion (UNaV), and urine flow (V) than rats with denervated kidneys. Also, renal denervation shifted pressure-diuresis and natriuresis toward lower pressures. A low dose of N(omega)-nitro-L-arginine methyl esther (NAME, 3.7 nmol/kg per min) reduced UNaV and the fractional excretion of sodium (FENa) and blunted pressure-natriuresis only in rats with innervated kidneys, whereas it had no effects in rats with denervated kidneys. A medium dose of NAME (37 nmol/kg per min) lowered FENa only in rats with innervated kidneys. The administration of NAME (37 nmol/kg per min) blunted pressure-diuresis and natriuresis in kidneys with or without the renal nerves, but the effect was more pronounced in rats with innervated kidneys. A high dose of NAME (3.7 micromol + 185 nmol/kg per min) increased UNaV and FENa only in rats with innervated kidneys, whereas it reduced GFR, V, UnaV, and FENa in rats with denervated kidneys. However, pressure-natriuresis and diuresis were blunted by this high dose of NAME independently of the presence or absence of renal nerves. These results demonstrate that renal nerves potentiate the renal effects of low doses of NAME on renal function and pressure-diuresis and natriuresis. However, high doses of NAME abolish pressure-diuresis independently of renal nerves, and the natriuretic effect of NAME in innervated kidneys may be attributed to reflex inhibition of sympathetic tone due to the rise in arterial pressure.

Effects of N omega-nitro-L-arginine and N-acetyl-L-cysteine on the reversal of one-kidney, one-clip hypertension.

The present study evaluated whether nitric oxide (NO) synthesis blockade or potentiation (with N omega-nitro-L-arginine or N-acetyl-L-cysteine, respectively) modulates the systemic and renal responses to unclipping in anesthetized one-kidney, one-clip hypertensive rats (1K-1C). Cardiac output was measured by thermodilution. In time-control rats, mean arterial pressure (MAP) decreased from 197 +/- 8 mm Hg to 139 +/- 4 mm Hg 3 h after unclipping, and cardiac index (CI) decreased by 35%, with a transient rise in sodium and water excretion and no changes in total peripheral resistance (TPR), glomerular filtration rate (GFR), or renal plasma flow (RPF). Administration of N omega-nitro-L-arginine methyl ester (NAME, 10 micrograms/kg/ min) blunted the hypotensive (from 190 +/- 6 mm Hg to 157 +/- 3 mm Hg), diuretic and natriuretic responses and potentiated the decrease in CI (40%) observed after unclipping, whereas TPR increased by 103%. Also, in rats given NAME, GFR and RPF decreased by 20% and 45%, respectively, at the end of the experiment. The effect of N-acetyl-L-cysteine (NAC, 300 mg/kg), a sulfhydryl group donor that may protect NO from free radical destruction by forming an S-nitrosothiol compound, was also evaluated. NAC potentiated the depressor response to unclipping (from 180 +/- 5 mm Hg to 97 +/- 3 mm Hg), and GFR and RPF increased by 80% and 35%, respectively. These effects of NAC appear to be NO dependent, as they were blocked by simultaneous administration of NAME. However, no significant differences were observed among groups in cumulative excretion of sodium and water, demonstrating that the hemodynamic effects of NAME and NAC after unclipping are due to mechanisms other than renal excretory changes. The results of the present study indicate that the cardiovascular depressor effects of unclipping are modulated by endothelium-derived nitric oxide.

Effect of interactions between nitric oxide and angiotensin II on pressure diuresis and natriuresis.

The present study examined the effect of an angiotensin II AT1 or AT2 receptor antagonist on the impairment of the pressure diuresis and natriuresis response produced by nitric oxide (NO) synthesis blockade. N omega-nitro-L-arginine methyl ester (L-NAME, 37 nmol.kg-1.min-1) lowered renal blood flow and reduced the slopes of the pressure diuresis and natriuresis responses by 44 and 40%, respectively. Blockade of AT1 receptors with valsartan increased slightly sodium and water excretion at low renal perfusion pressure (RPP). Blockade of AT2 receptors with PD-123319 had no effect on renal function. The administration of valsartan or PD-123319 to rats given L-NAME had no effect on the renal vasoconstriction induced by NO synthesis blockade. In addition, in rats given L-NAME, valsartan elevated baseline excretory values at all RPP studied, but it had no effect on the sensitivity of the pressure diuresis and natriuresis response. However, the administration of PD-123319 to L-NAME-pretreated rats shifted the slopes of the pressure diuresis and natriuresis responses toward control values, indicating that the impairment produced by NO synthesis blockade on pressure diuresis is dependent on the activation of AT2 angiotensin receptors.

Interactions between nitric oxide and angiotensin II on renal cortical and papillary blood flow.

This study examined the role of angiotensin II (Ang II) on the effects of nitric oxide (NO) synthesis blockade on renal cortical and papillary blood flow in innervated and denervated kidneys of volume-expanded Munich-Wistar rats with hormonal influences on the kidney that were held constant by intravenous infusion. Cortical (CBF) and papillary (PBF) blood flow were measured by laser-Doppler flowmetry. A low dose of N omega-nitro-L-arginine methyl ester (L-NAME, 3.7 nmol x kg[-1] x min[-1]) reduced CBF only in innervated kidneys, and this effect was abolished by subsequent administration of valsartan (an AT1 antagonist). L-NAME 3.7 nmol x kg(-1) x min(-1) improved PBF autoregulation by lowering PBF to the range of 100 to 140 mm Hg of perfusion pressure, and this effect was attenuated or abolished by valsartan in innervated and denervated kidneys, respectively. These results indicate that the cortical and medullary vasoconstriction induced by a low dose of L-NAME are caused by potentiation of the vasoconstrictor influence of renal sympathetic nerves and Ang II. A higher dose of L-NAME (37 nmol x kg[-1] x min[-1]) lowered CBF and PBF in both innervated and denervated kidneys. This effect of L-NAME on the cortical circulation was abolished by valsartan, but this AT1 antagonist had no effect on the medullary vasoconstriction produced by NO synthesis blockade. Therefore, a higher dose of L-NAME induces a renal cortical vasoconstriction through potentiation of the renin-angiotensin system, whereas the fall of PBF seen after L-NAME 37 nmol x kg(-1) x min(-1) seems to be caused primarily by NO suppression. This Ang II potentiation produced by L-NAME in the renal cortex seems to be mediated by AT1 receptors, because it was unaffected by PD123319 (an AT2 antagonist). The results of the present study indicate that NO is an important modulator of the vasoconstrictor influence of Ang II in the renal cortical circulation of the rat. However, although there are some interactions between NO and renal nerves and Ang II on the medullary circulation, the renal medullary vasoconstriction produced by L-NAME appears to be caused primarily by NO suppression, with little influence of the renal vasoconstrictor systems.

[Current treatment and prevention of juvenile gastroenteritis]. / Actualización del tratamiento y prevención de la gastroenteritis infantil.

The present knowledges about the damage mechanisms of germs in infectious diarrhea, on which are based the therapy procedures are reviewed. The management consist in oral rehydratation and precocius oral feeding as the main therapy. A scheme of treatment and the future perspectives in Valladolid during the last 9 months (609 fecal cultures) is reported. The participation of isolated germs in the pathogenesis of diarrhea is discussed. Since the acquisition of new methods to detect compylobacter, yersinia and rotavirus, the number of positive fecal cultures has increased in our medium.