HYPOTENSIVE EFFECT OF CHRONICALLY INFUSED ADRENOMEDULLIN IN CONSCIOUS WISTAR-KYOTO AND SPONTANEOUSLY HYPERTENSIVE RATS

1. The hypotensive effect of chronically infused human adrenomedullin (hAM), a potent vasodilator peptide that has been reported to have a natriuretic action, was examined in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). 2. Conscious WKY rats and SHR were infused with 200 ng/h synthetic hAM for 14 days by means of osmotic minipumps. Control groups were infused at the same schedule with 0.9% saline. Systolic blood pressure (SBP) and daily urinary excretion of Na⁺ and K⁺ were measured before and during the infusion period. In addition, plasma renin activity (PRA), aldosterone and hAM concentrations were measured on day 14 of infusion. 3. A significant reduction in SBP was observed in hAM-treated SHR at day 2 and SBP remained significantly lower throughout the experiment compared with control SHR. Similarly, SBP in the hAM-treated WKY rats was found to be significantly lower than in control WKY rats during infusion. However, the hypotensive effect was not accompanied by any significant increase in urinary volume or Na⁺ excretion in hAM-treated rats of either strain. Chronic infusion with hAM significantly suppressed PRA and lowered the concentration of plasma aldosterone in WKY rats but not in SHR. The plasma hAM levels in treated WKY rats and SHR were 0.0 ± 9.4 and 0.6 ± 0.2 fmol/mL, respectively. 4. These findings demonstrate that chronically infused hAM has a hypotensive effect in both WKY rats and SHR without an increase in urinary volume or Na⁺ excretion at a plasma AM concentration within the physiological limit.