Kidney renin gene expression after renin inhibition in the marmoset.
1. The effects of renin inhibitor ES-8891 on renin synthesis and its secretion by the kidney were investigated in normotensive sodium-depleted marmosets. We measured plasma renin activity, plasma immunoreactive renin concentration, plasma angiotensin II concentration and kidney renin mRNA content after oral administration of ES-8891 (60 mg day-1 kg-1) for 1 week. 2. The mean blood pressure was significantly decreased (P less than 0.01) on day 7 after oral administration of ES-8891. There was no significant change in heart rate during the administration. 3. Oral administration of ES-8891 for 1 week markedly decreased the plasma renin activity, the plasma immunoreactive renin concentration and the plasma angiotensin II concentration (to 18%, 41% and 24% of the corresponding control values; P less than 0.05 for each, n = 5). 4. The kidney renin mRNA content in ES-8891-treated marmosets was significantly lower than that in normal controls (4.2 +/- 3.5 versus 12.8 +/- 5.5 pg/micrograms of total RNA, means +/- SD, P less than 0.05, n = 5). 5. Oral administration of the renin inhibitor ES-8891 for 1 week not only inhibited plasma renin activity but also decreased renin synthesis and its secretion by the kidney.
Kitami
Y
Y
2nd Department of Internal Medicine, Ehime University School of Medicine, Japan.
Hiwada
K
K
Murakami
E
E
Iwata
T
T
Muneta
S
S
Kokubu
T
T
D000804:Angiotensin II / Q000097:blood; D000818:Animals; D015152:Blotting, Northern; D002144:Callithrix; D015342:DNA Probes; D004151:Dipeptides / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D007668:Kidney / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D012083:Renin / Q000096:biosynthesis / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D000092502:Renin Inhibitors
D000804:Angiotensin II; D015342:DNA Probes; D004151:Dipeptides; D009025:Morpholines; D012333:RNA, Messenger; D012083:Renin; D000092502:Renin Inhibitors; C064483:ES 8891