2腎1クリップ高血圧ラットの初期昇圧における腎性降圧利尿系とウアバイン様因子の役割

抄録

Recent studies have shown that not only an enhanced renin-angiotensin system, but also relative volume retention might contribute to hypertension even in the early phase of a two kidney, one-clip hypertensive model. To evaluate the role of renal depressor and natriuretic systems in the development of high blood pressure in the early phase of this model, we measured urinary excretion of kallikrein (uKAL), prostaglandin E₂ (uPGE₂), and dopamine (uDA) in male Sprague-Dawley rats instrumented with a 0.2 mm diameter clip on the left renal artery (2K1C) and compared the results with those of sham-operated rats (sham). We also measured ouabain-like factor (OLF) in the plasma (pOLF) and urine (uOLF) in both groups. In 2K1C, systolic blood pressure (SBP) progressively increased and plasma renin activity was higher than the sham in the 3rd week. UDA and uPGE₂ were not different between these groups, but uKAL attenuated in 2K1C in the 1st and 3rd week compared to the sham. There was a negative correlation between %ΔSBP and %ΔuKAL. On the other hand, uOLF increased in 2K1C in the 1st, 2nd and 3rd week compared to the sham. There was a positive correlation between SBP and uOLF. And pOLF was higher in 2K1C than in the sham. Furthermore there was a negative correlation between %uKAL and %ΔuOLF. These results indicated that even in the early phase, suppression of the renal kallikrein-kinin system would contribute to high blood pressure in part, and OLF might play a compensatory role against the impaired natriuretic system in the kidney. However, OLF might contribute to blood pressure elevation through vasoconstriction in 2K1C.