The role of kinins and atrial natriuretic peptide on the renal effects of neutral endopeptidase inhibitor in normotensive and hypertensive rats.
To further elucidate the renal effects of NEP inhibition, we employed NEP inhibitor UK 73967 (UK), with or without a kinin receptor antagonist Hoe 140 (Hoe), in Sprague-Dawley normotensive rats and DOCA-salt hypertensive rats. In Sprague-Dawley rats: 1) injected UK significantly decreased NEP, and increased kinins, urine volume (UV) and urinary sodium excretion (UNaV), while none of the variables changed with vehicle treatment; 2) no difference was found in plasma ANP between the vehicle and UK groups; and 3) Hoe canceled the increases of UV and UNaV caused by UK. In DOCA-salt rats: 1) infused UK significantly decreased NEP, and increased UV and UNaV, while UV and UNaV were slightly decreased, and NEP did not change with vehicle treatment; 2) plasma ANP was significantly higher in UK group than in the vehicle group; and 3) Hoe could not abolish the increase of UV and UNaV induced by UK. These data indicate that the contributions of renal kinins and plasma ANP to the diuretic and natriuretic mechanisms of NEP inhibition may differ between Sprague-Dawley normotensive rats and DOCA-salt hypertensive rats.
Nomura
N
N
Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.
Shimamoto
K
K
Ura
N
N
Iwata
M
M
Aoyama
T
T
Takagawa
Y
Y
Iimura
O
O
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood*; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D003900:Desoxycorticosterone; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D007705:Kinins / Q000652:urine*; D008297:Male; D015260:Neprilysin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000319:Adrenergic beta-Antagonists; D003509:Cyclohexanecarboxylic Acids; D007705:Kinins; D011480:Protease Inhibitors; D003900:Desoxycorticosterone; C065679:icatibant; C060942:candoxatrilat; D009320:Atrial Natriuretic Factor; D015260:Neprilysin; D001920:Bradykinin