Effects of a neutral endopeptidase inhibitor, BP102, on the development of deoxycorticosterone acetate-salt hypertension in kininogen-deficient Brown Norway Katholiek rats.
The nature of all of the peptides critical to the mechanism(s) of the antihypertensive action of neutral endopeptidase (NEP) inhibitors is still unclear, but bradykinin is thought to be one such peptide. This study was designed to assess the effectiveness of an NEP inhibitor in deoxycorticosterone acetate (DOCA)-salt treated kininogen-deficient Brown Norway Katholiek (BN-Ka) rats. Oral administration of BP102 (10-100 mg/kg), an NEP inhibitor, increased urine volume and urinary sodium excretion in a dose-dependent manner in anesthetized Sprague-Dawley rats. DOCA-salt hypertension was induced in both BN-Ka and Brown Norway Kitasato (BN-Ki) rats after left nephrectomy. The development of DOCA-salt hypertension in normal BN-Ki rats was prevented, and that in BN-Ka rats was also significantly reduced, by an 8-day administration of BP102. When BP102 was administered for 5 weeks, the high blood pressure of DOCA-salt treated BN-Ka rats was markedly lowered, and their heart weights were reduced. These results suggest that kinins play no role in the antihypertensive effect of this inhibitor and that other factors may be involved in this effect.
Nakajima
S
S
Department of Internal Medicine, Kitasato University School of Medicine, Kanagawa, Japan.
Majima
M
M
Ito
H
H
Hayashi
I
I
Yajima
Y
Y
Katori
M
M
D000284:Administration, Oral; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D003900:Desoxycorticosterone; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000201:enzymology / Q000209:etiology*; D007668:Kidney / Q000187:drug effects; D007704:Kininogens / Q000097:blood / Q000172:deficiency* / Q000235:genetics*; D007705:Kinins / Q000652:urine; D008297:Male; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D009929:Organ Size / Q000187:drug effects; D011355:Prodrugs / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011914:Rats, Inbred BN; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride; D015244:Thiorphan / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D004791:Enzyme Inhibitors; D007704:Kininogens; D007705:Kinins; D011355:Prodrugs; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D009320:Atrial Natriuretic Factor; D015244:Thiorphan; D015260:Neprilysin