Attenuated glomerular arginine transport prevents hyperfiltration and induces HIF-1α in the pregnant uremic rat.

Pregnancy worsens renal function in females with chronic renal failure (CRF) through an unknown mechanism. Reduced nitric oxide (NO) generation induces renal injury. Arginine transport by cationic amino acid transporter-1 (CAT-1), which governs endothelial NO generation, is reduced in both renal failure and pregnancy. We hypothesize that attenuated maternal glomerular arginine transport promotes renal damage in CRF pregnant rats. In uremic rats, pregnancy induced a significant decrease in glomerular arginine transport and cGMP generation (a measure of NO production) compared with CRF or pregnancy alone and these effects were prevented by l-arginine. While CAT-1 abundance was unchanged in all experimental groups, protein kinase C (PKC)-α, phosphorylated PKC-α (CAT-1 inhibitor), and phosphorylated CAT-1 were significantly augmented in CRF, pregnant, and pregnant CRF animals; phenomena that were prevented by coadministrating l-arginine. α-Tocopherol (PKC inhibitor) significantly increased arginine transport in both pregnant and CRF pregnant rats, effects that were attenuated by ex vivo incubation of glomeruli with PMA (a PKC stimulant). Renal histology revealed no differences between all experimental groups. Inulin and p-aminohippurate clearances failed to augment and renal cortical expression of hypoxia inducible factor-1α (HIF-1α) significantly increased in CRF pregnant rat, findings that were prevented by arginine. These studies suggest that in CRF rats, pregnancy induces a profound decrease in glomerular arginine transport, through posttranslational regulation of CAT-1 by PKC-α, resulting in attenuated NO generation. These events provoke renal damage manifested by upregulation of renal HIF-1α and loss of the ability to increase glomerular filtration rate during gestation.

Hyperuricemia attenuates aortic nitric oxide generation, through inhibition of arginine transport, in rats.

OBJECTIVES: Hyperuricemia provokes endothelial dysfunction (ECD). Decreased endothelial nitric oxide synthase (eNOS) activity is an important source of ECD. Cationic amino acid transporter-1 (CAT-1) is the specific arginine transporter for eNOS. We hypothesize that hyperuricemia inhibits arginine uptake. METHODS: Experiments were performed in freshly harvested aortas from untreated animals and rats fed with oxonic acid (hyperuricemia), and compared to hyperuricemic rats treated with either allopurinol, benzbromarone or arginine. RESULTS: Arginine transport was significantly decreased in hyperuricemia. Benzbromarone and arginine prevented the decrease in arginine transport in hyperuricemic rats while allopurinol did not. Arginine transport was significantly decreased in control rats treated with allopurinol. Blood pressure response to acetylcholine was significantly attenuated in hyperuricemic rats, an effect which was prevented in all other experimental groups. L-NAME inhibitable cGMP response to carbamyl-choline was significantly decreased in hyperuricemic rats and this was completely prevented by both benzbromarone and arginine, while allopurinol partially prevented the aforementioned phenomenon. Hyperuricemia induced a significant increase in protein nitration that was prevented by benzbromarone, allopurinol, and arginine. Protein abundance of CAT-1, PKCα, and phosphorylated PKCα remained unchanged in all experimental groups. CONCLUSIONS: In hyperuricemia, the decrease in aortic eNOS activity is predominantly the result of attenuated arginine uptake.

Correlation between adherence to precautions issued by the WHO and diarrhea among long-term travelers to India.

BACKGROUND: Travelers' diarrhea is the most common infectious disease afflicting travelers to developing countries. Most studies investigating the benefits of recommendations regarding the consumption of food and water have focused on short-term travelers. We investigated the benefits of adherence to the precautions from the World Health Organization (WHO) among long-term travelers. METHODS: We asked 140 incidental travelers in India traveling for at least 2 months to complete a questionnaire about their adherence to the WHO precautions and the occurrence of diarrhea. Adherence was graded on a scale of 1 to 6 (least to most). RESULTS: The mean age of the 114 travelers whose questionnaires were eligible was 26.6 +/- 5.7 years, and the median duration of their trip was 5 months. None of them adhered strictly to the entire set of rules. The mean individual adherence was 3.4 (range 1.2-5.8). The vast majority of the travelers (83%) suffered from diarrhea. Most travelers (60%) had diarrhea for up to 3% of their journey time. Diarrhea was accompanied by fever among 18% and necessitated hospitalization in 3%. Forty-five percent indicated that they had lost traveling days due to diarrhea, for an average of 0.7% of the traveling time. We found no correlation between the percentage of traveling time with diarrhea and the following variables: adherence to the WHO recommendations, receipt of advice regarding prevention, duration of the trip, age, sex, and nationality of the travelers. CONCLUSIONS: Dietary self-restraint of travelers as proposed by the WHO is both difficult to comply with and lacks a proven value for the long-term traveler to a developing country.