The natriuretic mechanisms of neutral endopeptidase inhibitor in rats.
The activity of the renal kallikrein-kinin system is controlled by the concentration of intrarenal kinins. Neutral endopeptidase 24.11 (NEP) cleaves kinins as effectively as kininase I and kininase II. It is also well known that NEP metabolizes atrial natriuretic peptide (ANP). The present study evaluated the effects of NEP inhibitor on renal action by kinins, ANP and nitric oxide in Sprague-Dawley normotensive rats and DOCA-salt hypertensive rats. In normotensive rats, we demonstrated that 1) inhibition of NEP potentiates the contribution of kinins to the renal water-sodium metabolism and overcomes the contribution of ANP to that metabolism, 2) nitric oxide participates in the action of kinins, and 3) changes in urinary cGMP excretion do not reflect the changes in plasma ANP, but the changes in nitric oxide, under these conditions. On the other hand, it was also suggested that augmented ANP may contribute mainly to renal water-sodium handling by NEP inhibitor in DOCA-salt rats. Therefore, the contributions of the two systems to the diuretic and natriuretic mechanisms of NEP inhibition may differ between Sprague-Dawley normotensive rats and DOCA-salt hypertensive rats.
Shimamoto
K
K
Second Department of Internal Medicine, Sapporo Medical University, School of Medicine, Japan.
Ura
N
N
Iimura
O
O
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006152:Cyclic GMP / Q000652:urine; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D004231:Diuresis / Q000187:drug effects; D016234:Kallikrein-Kinin System / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D007705:Kinins / Q000378:metabolism; D009318:Natriuresis / Q000187:drug effects; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000652:urine
D003509:Cyclohexanecarboxylic Acids; D007705:Kinins; C065679:icatibant; C060942:candoxatrilat; D009320:Atrial Natriuretic Factor; D012964:Sodium; D015260:Neprilysin; D006152:Cyclic GMP; D001920:Bradykinin