Effects of atrial natriuretic peptide on the extrasplenic microvasculature and lymphatics in the rat in vivo

We developed a novel model using fluorescent intravital microscopy to study the effect of atrial natriuretic peptide (ANP) on the extrasplenic microcirculation. Continuous infusion of ANP into the splenic artery (10 ng min −1 for 60 min) of male Long–Evans rats (220–250 g, n = 24) induced constriction of the splenic arterioles after 15 min (−7.2 ± 6.6% from baseline diameter of 96 ± 18.3 μm, mean ± s.e.m. ) and venules (−14.4 ± 4.0% from 249 ± 25.8 μm; P < 0.05). At the same time flow did not change in the arterioles (from 1.58 ± 0.34 to 1.27 ± 0.27 ml min −1 ), although it decreased in venules (from 1.67 ± 0.23 to 1.15 ± 0.20 ml min −1 ) and increased in the lymphatics (from 0.007 ± 0.001 to 0.034 ± 0.008 ml min −1 ; P < 0.05). There was no significant change in mean arterial pressure (from 118 ± 5 to 112 ± 5 mmHg). After continuous ANP infusion for 60 min, the arterioles were dilated (108 ± 16 μm, P < 0.05) but the venules remained constricted (223 ± 24 μm). Blood flow decreased in both arterioles (0.76 ± 0.12 ml min −1 ) and venules (1.03 ± 0.18 ml min −1 ; P < 0.05), but was now unchanged from baseline in the lymphatics (0.01 ± 0.001 ml min −1 ). This was accompanied by a significant decrease in MAP (104 ± 5 mmHg; P < 0.05). At 60 min, there was macromolecular leak from the lymphatics, as indicated by increased interstitial fluorescein isothiocyanate–bovine serum albumin fluorescence (grey level: 0 = black; 255 = white; from 55.8 ± 7.6 to 71.8 ± 5.9, P < 0.05). This study confirms our previous proposition that, in the extrasplenic microcirculation, ANP causes greater increases in post- than precapillary resistance, thus increasing intrasplenic capillary hydrostatic pressure ( P c ) and fluid efflux into the lymphatic system. Longer-term infusion of ANP also increases Pc, but this is accompanied by increased ‘permeability’ of the extrasplenic lymphatics, such that fluid is lost to perivascular third spaces.