Renal ischemia induces an increase in nitric oxide levels from tissue stores.

Tissue nitric oxide (NO) levels increase dramatically during ischemia, an effect that has been shown to be partially independent from NO synthases. Because NO is stored in tissues as S-nitrosothiols and because these compounds could release NO during ischemia, we evaluated the effects of buthionine sulfoximine (BSO; an intracellular glutathione depletor), light stimulation (which releases NO, decomposing S-nitrosothiols), and N-acetyl-L-cysteine (a sulfhydryl group donor that repletes S-nitrosothiols stores) on the changes in outer medullary NO concentration produced during 45 min of renal artery occlusion in anesthetized rats. Renal ischemia increased renal tissue NO concentration (+223%), and this effect was maintained along 45 min of renal arterial blockade. After reperfusion, NO concentration fell below preischemic values and remained stable for the remainder of the experiment. Pretreatment with 10 mg/kg nitro-L-arginine methyl ester (L-NAME) decreased significantly basal NO concentration before ischemia, but it did not modify the rise in NO levels observed during ischemia. In rats pretreated with 4 mmol/kg BSO and L-NAME, ischemia was followed by a transient increase in renal NO concentration that fell to preischemic values 20 min before reperfusion. A similar response was observed when the kidney was illuminated 40 min before the ischemia. The coadministration of 10 mg/kg iv N-acetyl-L-cysteine with BSO + L-NAME restored the increase in NO levels observed during renal ischemia and prevented the depletion of renal thiol groups. These results demonstrate that the increase in renal NO concentration observed during ischemia originates from thiol-dependent tissue stores.

Evaluation of the safety and immunogenicity of pneumococcal seven-valent conjugate vaccine (Prevenar) administered in previously unvaccinated Spanish children aged 24 to 36 months.

This study evaluates the safety and immunogenicity of pneumococcal seven-valent conjugate vaccine (Prevenar) in 115 children, aged 2-3 years (24-36 months), who have not been previously vaccinated with Prevenar. SAFETY: As for local reactions, 40% of children reported erythema, 32.2% induration and 39.1% tenderness at the injection site. Regarding systemic reactions, fever > or 38 C was recorded in 7% of patients. Other commonly reported events were decreased appetite (24.3%), restlessness (20%), and fussiness (18.3%). IMMUNOGENICITY: After vaccination, more than 98% of the subjects achieved antibody levels of > or = 0.15 microg/mL for all seven serotypes and more than 95% achieved antibody levels > or = 0.50 microg/mL for all serotypes. CONCLUSIONS: Pneumococcal seven-valent conjugate vaccine (Prevenar) was safe, well tolerated and highly immunogenic when administered in previously unvaccinated children aged 14-36 months.

Acute renal hemodynamic effects of dimanganese decacarbonyl and cobalt protoporphyrin.

BACKGROUND: Heme oxygenase (HO) products have a protective role in acute renal failure (ARF) that may be hemodynamically mediated because the HO-derived carbon monoxide (CO) is an important control system of arteriolar tone. The vascular effects of HO may be caused directly through changes in CO synthesis, and indirectly by alterations in nitric oxide (NO) release. The present study evaluated in vivo the renal effects of a heme oxygenase inhibitor, Co(III)Protoporphyrin (CoPP) alone or in combination with the CO donor dimanganese decacarbonyl (Mn2(CO)10). METHODS: All drugs were administered into the renal artery of anesthetized rats. Changes in renal cortical nitric oxide concentration were measured in vivo electrochemically. RESULTS: The intrarenal administration of the CO donor Mn2(CO)10 increased blood carboxyhemoglobin levels (+74%), renal blood flow (+54%), glomerular filtration (+38%), and urinary cGMP excretion (+128%). On the other hand, the inhibition of renal HO with CoPP progressively induced an ARF characterized by a drop in renal blood flow (-77%), glomerular filtration (-93%), and urinary cGMP excretion (-93%). These deleterious effects of HO inhibition on renal function were nearly abolished by supplementing CO with the coadministration of Mn2(CO)10+ CoPP, indicating that they may be caused by inhibition of CO synthesis and the resulting hemodynamic changes. In addition, CoPP lowered the renal cortical NO concentration (-21%) and also decreased the urinary excretion of nitrates/nitrites, while Mn2(CO)10 increased renal NO levels (+20%) and raised the excretion of nitrates/nitrites, suggesting that changes in NO release may contribute to the renal effects of the HO-CO system. CONCLUSION: These results indicate that heme oxygenase-derived CO plays a cardinal role in the control of renal hemodynamics and glomerular filtration.

Role of superoxide in modulating the renal effects of angiotensin II.

Angiotensin II is known to stimulate NADPH oxidase-dependent superoxide (O2-) generation, which may contribute to the acute renal vasoconstrictor and antinatriuretic actions of this peptide. To evaluate this hypothesis, the effects of a superoxide dismutase mimetic (tempol) or a NADPH inhibitor (apocynin) on the angiotensin renal actions were studied. Renal cortical nitric oxide (NO) was measured electrochemically in vivo. Tempol increased sodium excretion and NO levels. Apocynin raised renal blood flow, glomerular filtration rate, sodium excretion, and NO levels. These results indicate the presence of an endogenous NADPH oxidase-dependent O2- generation that may modulate renal function by scavenging NO. Angiotensin II infusion reduced renal blood flow, glomerular filtration, sodium excretion, and NO levels in a dose-dependent manner. The angiotensin receptor antagonist valsartan, tempol, or apocynin blunted the angiotensin effects on renal excretion and NO, suggesting that angiotensin receptors stimulation induces the NADPH oxidase-dependent O2- generation that might reduce NO bioavailability. This idea is supported by the finding that angiotensin increased O2- generation in renal homogenates, and this effect was prevented by valsartan, apocynin, or tempol. These results indicate that some of the acute renal effects of angiotensin II may be enhanced by an increased NADPH oxidase-derived O2- production that reduces renal NO bioavailability.