Effects of renin inhibitors on the expression of kidney renin gene and tissue renin-like activity.
The effect of renin inhibitor ES-1005 on renin gene expression was investigated in sodium-depleted marmosets. The kidneys were removed after continuous infusion of ES-1005 (12 mg/kg per h) for 2 h. The relative amount of kidney renin messenger (m)RNA was measured by densitometric Northern blot analysis using an alpha-32P-labelled human renin complementary (c)DNA fragment as a hybridization probe. Plasma renin activity was completely inhibited by ES-1005. The level of kidney renin mRNA decreased significantly to about one-third of the normal control value. We also investigated the inhibitory potency of the renin inhibitor ES-6864 on the renin-like activity in dog tissues (adrenal glands, aorta and brainstem). ES-6864 inhibited the tissue renin-like activity with an IC50 of 10(-7) to 10(-8) mol/l in vitro. Renin inhibitors not only inhibit the activity of plasma and tissue renin, but also suppress the synthesis of renin in the kidney.
Kokubu
T
T
Kinki Central Hospital, Hyogo, Japan.
Kitami
Y
Y
Muneta
S
S
Murakami
E
E
Hiwada
K
K
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015152:Blotting, Northern; D002144:Callithrix; D002216:Captopril / Q000494:pharmacology; D004285:Dogs; D005260:Female; D007668:Kidney / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects*; D012083:Renin / Q000235:genetics / Q000378:metabolism; D012964:Sodium / Q000172:deficiency; D000092502:Renin Inhibitors
D002216:Captopril; D009842:Oligopeptides; D012333:RNA, Messenger; D012083:Renin; D012964:Sodium; D000092502:Renin Inhibitors; C056080:ES 1005