Effect of chronically infused adrenomedullin in two-kidney, one-clip hypertensive rats.
The hypotensive effect of chronically infused adrenomedullin, a potent vasodilator peptide, was examined in conscious two-kidney, one-clip (2K-1C) hypertensive and sham-operated rats. They were infused with 1.0 microgram/h of synthetic human adrenomedullin for 14 days by means of osmotic minipumps. Control groups were infused on the same schedule with 0.9% saline. Systolic blood pressure was measured before and during the infusion. Plasma renin activity, aldosterone and human adrenomedullin concentrations were determined at day 14 of the infusion. A significant reduction of systolic blood pressure was observed in the adrenomedullin-infused 2K-1C rats at day 4, and systolic blood pressure remained significantly lower throughout the experiment compared to that of the control 2K-1C. A similar hypotensive effect was seen in the adrenomedullin-infused sham-operated rats. Both the plasma renin activity and aldosterone concentrations of the adrenomedullin-infused 2K-1C and sham groups were significantly reduced compared to those of the respective control, whereas, the plasma human adrenomedullin concentration in the adrenomedullin-infused groups was found to be within the physiological range. These findings demonstrated that chronically infused adrenomedullin had a hypotensive effect accompanied by significant reductions of plasma renin activity and plasma aldosterone concentration in 2K-1C hypertensive and sham-operated rats.
Khan
A I
AI
First Department of Internal Medicine, Miyazaki Medical College, Japan.
Kato
J
J
Ishiyama
Y
Y
Kitamura
K
K
Kangawa
K
K
Eto
T
T
D053607:Adrenomedullin; D000450:Aldosterone / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D006978:Hypertension, Renovascular / Q000188:drug therapy*; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects / Q000601:surgery; D016014:Linear Models; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood; D014665:Vasodilator Agents / Q000494:pharmacology*
D000959:Antihypertensive Agents; D010455:Peptides; D014665:Vasodilator Agents; D053607:Adrenomedullin; D000450:Aldosterone; D012083:Renin