The role of kinins and atrial natriuretic peptide on the renal effects of neutral endopeptidase inhibitor in rats.
To further elucidate the natriuretic mechanisms of neutral endopeptidase 24.11 (NEP) inhibition, we employed a new specific NEP inhibitor, UK 73967 (UK), with or without a specific kinin receptor antagonist, Hoe 140 (Hoe), in Sprague-Dawley rats, and evaluated the renal NEP, kinins and plasma ANP simultaneously. There were no significant changes in urinary NEP, kinins, urine volume (UV) or urinary sodium excretion (UNaV) with vehicle treatment in anesthetized normotensive rats. Infused UK (10 mg/kg) significantly decreased NEP, and increased kinins, UV and UNaV. There was not a significant difference in plasma ANP between the vehicle and UK groups. Simultaneous administration of Hoe (20 nmol/kg) canceled the increases of UV and UNaV caused by UK. From these results, we conclude that inhibition of NEP may exaggerate the contribution of renal kinins to the renal water-sodium metabolism and overcome the contribution of ANP on that metabolism at least in normotensive rats.
Ura
N
N
Second Department of Internal Medicine, School of Medicine, Sapporo Medical University, Japan.
Shimamoto
K
K
Kuroda
S
S
Nomura
N
N
Iwata
M
M
Aoyama
T
T
Iimura
O
O
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007705:Kinins / Q000378:metabolism*; D008297:Male; D009318:Natriuresis / Q000187:drug effects / Q000502:physiology; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley
D003509:Cyclohexanecarboxylic Acids; D007705:Kinins; C065679:icatibant; C060942:candoxatrilat; D009320:Atrial Natriuretic Factor; D015260:Neprilysin; D001920:Bradykinin