Adrenomedullin increases fluid extravasation from the splenic circulation of the rat

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Abstract
We studied the effect of adrenomedullin (ADM) on fluid efflux from the splenic vasculature into extravascular spaces. Splenic arterial infusion of ADM (1, 3 and 9 ng min−1; n = 9, 11 and 10, respectively) caused a dose‐dependent increase in intrasplenic fluid efflux (+0.6 ± 0.3 (saline) vs.+2.0 ± 0.3 ml min−1 (9 ng min−1 ADM), P < 0.05), and in splenic (venous minus arterial) haematocrit (+0.8 ± 0.1 (saline, n = 6) vs.+3.1 ± 0.3 % (9 ng min−1 ADM, n = 7), P < 0.05). There was no change in splenic weight (0.99 ± 0.02 (saline, n = 6) vs. 0.99 ± 0.02 g (9 ng min−1 ADM, n = 7), P > 0.05). There was no change in MAP before (97.5 ± 2.2 mmHg), during (98.4 ± 3.4 mmHg), or after (100.2 ± 2.2 mmHg) intrasplenic infusion of ADM (9 ng min−1) (n = 11, P < 0.05). ADM (9 ng min−1) caused an increase in intrasplenic microvascular pressure (11.3 ± 0.3 (saline, n = 5) vs. 13.0 ± 0.3 mmHg (9 ng min−1 ADM, n = 6), P < 0.05). ADM (1 × 10−11 to 1 × 10−6m) induced greater vasorelaxation of isolated preconstricted splenic resistance arteries than veins (maximal relaxation: 60 ± 0.9 (artery, n = 9) vs. 43 ± 1.7 % (vein, n = 8), P < 0.05). l‐NMMA (10−4m) partially inhibited the ADM‐induced relaxation in splenic arteries (maximal relaxation: 38 ± 3 (ADM +l‐NMMA, n = 5) vs. 60 ± 3 % (ADM +d‐NMMA, n = 5), P < 0.05). It is concluded that ADM increases fluid efflux from the splenic vasculature by differentially reducing pre‐ vs. post‐capillary resistance, thus increasing intrasplenic microvascular pressure.