Effect of AVP.V1-receptor antagonist on urinary albumin excretion and renal hemodynamics in NIDDM nephropathy: role of AVP.V1-receptor.
We examined the effect of an orally effective, nonpeptide AVP.V1-receptor antagonist, OPC21268, on urinary albumin excretion and renal hemodynamics in non-insulin dependent diabetes mellitus (NIDDM) patients (seven patients with microalbuminuria, four with overt nephropathy, and three with normoalbuminuria) and in three normal subjects. The oral administration of 100 mg of OPC21268, which is sufficient to suppress the vasoconstriction induced by exogenously infused AVP, caused a significant decrease in urinary albumin excretion only in NIDDM with microalbuminuria concomitantly with a slight decrease in filtration fraction and glomerular filtration rate (GFR). On the other hand, urinary beta 2 microglobulin excretion did not change at all during the study. Neither change in systemic blood pressure, in heart rate, nor in plasma vasoactive substance levels (ANP, renin activity, aldosterone, and AVP) was observed in all four groups. In conclusion, in NIDDM patients with microalbuminuria, an increase in the sensitivity of contraction of glomerular efferent arterioles via an activation of AVP.V1-receptor(s) is at least present, and AVP.V1-receptor antagonist causes a decrease in urinary albumin excretion due partly to decrease the intraglomerular capillary pressure. This compound may be useful for the treatment of NIDDM microalbuminuria.
Yamada
K
K
Division of Clinical Research, Sakura National Hospital, Chiba, Japan.
Nakano
H
H
Nishimura
M
M
Yoshida
S
S
D000284:Administration, Oral; D000328:Adult; D000419:Albuminuria; D000450:Aldosterone / Q000097:blood; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology* / Q000652:urine; D003928:Diabetic Nephropathies / Q000503:physiopathology* / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D015363:Quinolones / Q000008:administration & dosage / Q000494:pharmacology*; D012016:Reference Values; D012079:Renal Circulation / Q000187:drug effects*; D012083:Renin / Q000097:blood; D014661:Vasoconstriction / Q000187:drug effects; D001613:beta 2-Microglobulin / Q000652:urine
D065092:Antidiuretic Hormone Receptor Antagonists; D010880:Piperidines; D015363:Quinolones; D001613:beta 2-Microglobulin; D001127:Arginine Vasopressin; C068644:OPC 21268; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D012083:Renin