EFFECT OF CHRONICALLY INFUSED ADRENOMEDULLIN IN 2-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 mu g/h of synthetic human adrenomedullin for 14 days by means of osmo tic 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 significa nt reduction of systolic blood pressure was observed in the adrenomedu llin-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 adrenomed ullin-infused sham-operated rats. Both the plasma renin activity and a ldosterone 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 th e adrenomedullin-infused groups was found to be within the physiologic al range. These findings demonstrated that chronically infused adrenom edullin had a hypotensive effect accompanied by significant reductions of plasma renin activity and plasma aldosterone concentration in 2K-1 C hypertensive and sham-operated rats. (C) 1997 Elsevier Science B.V.