| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1989: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1988: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1987: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
To assess the pathophysiological roles of atrial natriuretic factor (ANF) in hypertension, renal failure and heart failure, we determined circulating levels of ANF and the effects of synthetic ANF in rats experimental model of hypertension, chronic renal failure or chronic heart failure. We also examined the effects of synthetic ANF on cyclic GMP production in rat cultured vascular smooth muscle (VSM), glomerular mesangium (GM) and renal papillary collecting tubule (RPCT) cells to elucidate the mechanisms of vascular and renal actions of ANF. Elevated levels of circulating ANF were observed in spontaneously hypertensive rats (SHR) and DOCA- or aldosterone-salt hypertensive rats compared to control rats, respectively. The sustained infusion of synthetic ANF at a rate of subdepressor dose attenuated the hypertension in DOCA- or aldosterone-salt hypertension, but not in SHR. Circulating levels of ANF were also elevated in SHK or Wistar Kyoto rats remnant kidney model of chronic renal fail
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ure and in rats with chronic heart failure, induced by ligation of left coronary artery compared to control animals, respectively. In SHR with renal ablation, the sustained infusion of synthetic ANF induced a significant reduction of blood pressure, and the impaired renal function ameliorated. Angiotensin converting enzyme inhibitors also ameliorated renal function, which was associated with the decrease in circulating levels of ANF. In rats with chronic heart failure, the responses of natriuresis and diuresis to graded dosed of synthetic ANF were attenuated compared to control rats. In vitro studies, synthetic ANF increased cyclic GMP levels dose-dependently in cultured cells from rat renal and mesenteric VSM, GM and RPCT. The sensitivity of VSM and GM cells to synthetic ANF were greater than that RPCT cells.
These results suggest that ANF may play the protective roles in the pathophysioloqy of hypertension, chronic renal failure and chronic heart failure via its vascular and renal action. Less
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