Adrenomedullin increases fluid extravasation from the splenic circulation of the rat

Abstract

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.

Figure 1. Effect of ADM on splenic arterial (A) and venous (B) blood flows, and fluid efflux (C) (arterial – venous blood flow) from the spleen

ADM was infused into the splenic artery at doses of 0 (saline), 1, 3 and 9 ng min⁻¹(n = 11). Error bars indicate s.e.m. *P < 0.05 compared with saline-infused control group.

Figure 2. Effect of ADM on pre-capillary resistance (A), post-capillary resistance (B), and microvascular pressure (P_C, C) in the spleen

ADM was infused at a dose of 9 ng min⁻¹. Error bars indicate s.e.m. *P < 0.05, significant difference between saline-infused (n = 5) and ADM-infused (n = 6) groups.

Figure 3. Effect of ADM on vasorelaxation of splenic resistance arteries (•, n = 9) and veins (^, n = 8)

The vessels were preconstricted with phenylephrine (EC₈₀). *P < 0.05, significant difference between relaxation of artery and vein.

Figure 4. Effect of NO synthase inhibition on vasorelaxant activity of ADM on splenic resistance arteries

^, ADM plus l-NMMA (10⁻⁴m). •, ADM plus d-NMMA (10⁻⁴m). The vessels were preconstricted with phenylephrine (EC₈₀). *P < 0.05, significant difference between l-NMMA- and d-NMMA-treated groups.