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1 Department of Physiology, University of Alberta, Edmonton, Alberta, Canada, T6G 2S2
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 min1 for 60 min) of male LongEvans rats (220250 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 min1), although it decreased in venules (from 1.67 ± 0.23 to 1.15 ± 0.20 ml min1) and increased in the lymphatics (from 0.007 ± 0.001 to 0.034 ± 0.008 ml min1; 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 min1) and venules (1.03 ± 0.18 ml min1; P < 0.05), but was now unchanged from baseline in the lymphatics (0.01 ± 0.001 ml min1). 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 isothiocyanatebovine 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 (Pc) 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.
(Received 13 January 2005;
accepted after revision 15 February 2005;
first published online 17 February 2005)
Corresponding author Z. L. S. Brookes: University of Sheffield, Academic Unit of Anaesthesia, K Floor, Royal Hallamshire Hospital, Sheffield S10 2JF, UK. Email: zoe.brookes{at}sheffield.ac.uk
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