Antiproteinuric and Hyperkalemic Mechanisms Activated by Dual Versus Single Blockade of the RAS in Renovascular Hypertensive Rats

This study aimed to investigate the antiproteinuric and hyperkalemic mechanisms activated by dual renin-angiotensin system (RAS) blockade in renovascular hypertensive rats (2-kidney 1-clip model [2K-1C]). Six weeks after clipping the left renal artery or sham operation (2K), rats were treated with losartan, enalapril, or both drugs for two weeks. We found that 2K-1C rats displayed higher tail-cuff blood pressure (BP), increased non-clipped kidney Ang II concentration, and more pronounced urinary albumin excretion than 2K. BP was decreased by the treatment with either enalapril or losartan, and the combination of both drugs promoted an additional antihypertensive effect in 2K-1C rats. Renal Ang II content and albuminuria were reduced by either enalapril or losartan in monotherapy and restored to control levels by dual RAS blockade. Albuminuria in 2K-1C rats was accompanied by downregulation of the glomerular slit protein podocin, reduction of the endocytic receptors megalin and cubilin, and a marked decrease in the expression of the ClC-5 chloride channel, compared to 2K animals. Treatment with losartan and enalapril in monotherapy or combination increased the expression of podocin, cubilin, and ClC-5. However, only the combined therapy normalized podocin, cubilin, and ClC-5 protein abundance in the non-clipped kidney of 2K-1C rats. Renovascular hypertensive 2K-1C rats had a lower concentration of plasma potassium compared to 2K rats. Single RAS blockade normalized potassium plasma concentration, whereas 2K-1C rats treated with dual RAS blockade exhibited hyperkalemia. Hypokalemia in 2K-1C rats was accompanied by an increase in the cleaved activated forms of α-ENaC and γ-ENaC and the expression of β-ENaC. Combined RAS blockade but not monotherapy significantly reduced the expression of these ENaC subunits in 2K-1C rats. Indeed, double RAS blockade reduced the abundance of cleaved-α-ENaC to levels lower than those of 2K rats. Collectively, these results demonstrate that the antiproteinuric effect of dual RAS blockade in 2K-1C rats is associated with the restored abundance of podocin and cubilin, and ClC-5. Moreover, double RAS blockade-induced hyperkalemia may be due, at least partially, to an exaggerated downregulation of cleaved α-ENaC in the non-clipped kidney of renovascular hypertensive rats.

PENGARUH ORALIT WHO TERHADAP KADAR NATRIUM DAN KALIUM PLASMA PADA ANAK DIARE AKUT DENGAN DEHIDRASI

Acute diarrhea causes loss of large amounts of water and electrolytes especially sodium and potassium, which if not replaced can cause dehydration. In 2006, WHO recommended ORS with osmolarity 245 mmol/l as the administration of acute diarrhea with mild to moderate dehydration. The research objective is to determine the effect of WHO ORS to plasma sodium and potassium levels in children with acute diarrheal dehydration.Pre-experimental study with pre-post test approach absence of a control group, was conducted from November, 2012 until January, 2013 at Pediatric section RSUP.Prof.DR.RD.Kandou Manado. Sample 20 patients acute diarrhea mild to moderate dehydration. Pasien blood samples were taken to measure sodium and potassium plasma level before and after treatment with WHO ORS 75 cc/kg for three hours. Results electrolyte levels when dehydration 60% isonatremia and 85% isokalemia Electrolyte level when rehydration 70% isonatremia and 70% isokalemia. Sodium mean levels when dehydration 136.1±5.2 mmol/l and when rehydration 136.1±3.45 mmol/l with p=0.5. Potassium mean levels when dehydration 3.99±0.78 mmol/l and when rehydration 3.84±0.85 mmol/l with p=0.183. Conclusions: Most electrolyte levels before and after rehydration isonatremia and isokalemia. There is no significant differences in plasma sodium and potassium levels before and after rehydration with WHO ORS. Keywords Dehydration, Diarrhea, Potassium, Sodium, WHO ORS Abstrak: Diare akut menyebabkan hilangnya sejumlah besar air dan elektrolit terutama natrium dan kalium yang apabila tidak diganti dapat menyebabkan dehidrasi.Tahun 2006, WHO merekomendasikan oralit dengan osmolaritas 245 Mmol/l sebagai tata laksana diare akut dengan dehidrasi ringan sedang. Tujuan penelitian untuk mengetahui pengaruh oralit WHO terhadap kadar natrium dan kalium plasma pada anak diare akut dengan dehidrasi. Penelitian pra-eksperimental dengan pendekatan pre-post test tanpa adanya kelompok kontrol, berlangsung selama November 2012 sampai Januari 2013 di Bagian Ilmu Kesehatan Anak RSUP Prof.Dr.R.D.Kandou Manado. Sampel 20 pasien diare akut dehidrasi ringan sedang. Pasien diambil sampel darah untuk memeriksa kadar natrium dan kalium plasma sebelum dan sesudah terapi dengan oralit WHO 75 cc/kgbb selama tiga jam. Hasil didapatkan gambaran elektrolit saat dehidrasi terbanyak adalah isonatremia 60 % dan isokalemia 85%. Gambaran elektrolit saat rehidrasi terbanyak adalah isonatremia 70% dan isokalemia 70%. Rerata kadar Natrium saat dehidrasi adalah 136,1±5,2 mmol/L dan saat rehidrasi adalah 136,1±3,45mmol/l dengan p=0,5. Rerata kadar Kalium saat dehidrasi adalah 3,99±0,78mmol/l dan saat rehidrasi adalah 3,84±0,85mmol/l dengan p=0,183. Simpulan: Gambaran elektrolit sebelum dan sesudah rehidrasi terbanyak adalah isonatremia dan isokalemia.Tidak terdapat perbedaan bermakna kadar natrium dan kalium plasma sebelum dan sesudah rehidrasi dengan oralit WHO. Kata kunci Dehidrasi,Diare,Kalium,Natrium,Oralit WHO