Proteomic Analysis of Renal Kallikrein Pathway in Hypoxia Induced Hypertension

Obstructive sleep apnea syndrome (OSAS), a disorder characterized by episodic hypoxia (EH), is a major public health problem. OSAS affects 4-5% of the general adult population and 1-2% of children in the United States. One of the major consequences of untreated OSAS is systemic hypertension. In addition to hypertension, OSAS has also been associated with both proteinuria and end-stage renal disease. A rat model of EH was used to obtain proteins from the kidney after EH induction, which were resolved by two-dimensional PAGE and then identified by MALDI-MS (72). Proteomic analysis showed that EH induces changes in renal protein expression consistent with the impairment of vasodilation mediated by kallikrein-kallistatin pathway. However, transgenic rats expressing human tissue kallikrein were protected from EH-induced hypertension. The results obtained from kallikrein transgenic rats reinforce the proteomic data. Therefore, EH-induced hypertension may result, in part, from altered regulation of the renal KKS.

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