Dahl食塩感受性ラットの高血圧の成因に関わる腎kallikrein-kinin系,prostaglandin系の意義

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The Dahl salt-susceptible rat/John Rapp (SS/Jr) is a widely used animal model of salt-susceptible hypertension. However, it was reported that SS/Jr was genetically contaminated and was blunt to the pressor effect of a high salt diet. Independently, Iwai and Heine established new inbred Dahl SS and salt-resistant (SR) rat strains in 1986. In order to investigate the pathophysiolosical role of renal kallikrein-kinin, and prostaglandin systems in the development of hypertension in SS, urinary kallikrein excretion, and urinary prostaglandin E2 excretion were assessed in newly established Dahl salt-susceptible rats/Iwai (SS/Iwai) in comparison with those in Dahl saltresistant rats (SR/Iwai). SS/Iwai and SR/Iwai at the 4th week of age were housed individually in metabolic cages with regular chow (1% NaCl) for 1 week as a control period. They were placed on either a high (8%) (SS-H n=12; SR-H n=12) or a low (0.3%) (SS-L n=12; SR-L n=12) sodium chloride diet for an additional 3 weeks as an experimental period. Systolic blood pressure (SBP), urinary kallikrein excretion (KAL), and urinary prostaglandin E2 excretion (PGE2) were measured every week. After the three weeks as an experimental period, SBP of SS-H showed a significant (p<0.001) increase from 114±2 to 165±2 mmHg, and was significantly higher than in the other groups. Even in the control period, KAL was significantly (p<0.05) lower in SS/Iwai (129±10 μg/kg/day) than in SR/Iwai (178±9 μg/kg/day); the same tendency was also observed during the experimental period of high or low sodium diet. KAL was significantly increased during the high sodium diet in both SS-H and SR-H, while KAL of SS-H was significantly (p<0.05) lower than that of SR-H in the first week of high salt condition. There was no difference in PGE2 between SS/Iwai and SR/Iwai in the control period. However PGE2 significantly increased by salt load, and was significantly lower in SS-H than SR-H in the second week of the high salt condition. A significant negative correlation was found between SBP and KAL, and SBP and PGE2. Both KAL and PGE2 showed significant positive correlations between urine volume and urinary excretion of sodium. There was a significant positive correlation between KAL and PGE2. In conclusion, although renal KAL was responsible by salt load in Dahl/Iwai rats, the hereditarily suppressed renal KAL and successively suppressed renal PGE2 contribute to the salt induced blood pressure elevation in SS/Iwai rats.
札幌医科大学の論文
1998-08-01

Dahl食塩感受性ラットの高血圧の成因に関わる腎kallikrein-kinin系,prostaglandin系の意義

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