Adrenomedullin increases fluid extravasation from the splenic circulation of the rat

1. We studied the effect of adrenomedullin (ADM) on fluid efflux from the splenic vasculature into extravascular spaces. 2. 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). 3. 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). 4. 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). 5. ADM (1 x 10(-11) to 1 x 10(-6) M) 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(-4) M) 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). 6. 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.