Differential sensitivity of exchange vessel hydraulic conductivity to atria1 natriuretic peptide D. JOSEPH MEYER, JR. AND VIRGINIA H. HUXLEY Department of Physiology, University of Missouri School of Medicine, Columbia, Missouri 65212 MEYER, D. JOSEPH, JR., AND VIRGINIA H. HUXLEY. Differ- ential sensitivity of exchange vessel hydraulic conductivity to atrial natriuretic peptide. Am. J. Physiol. 258 (Heart Circ. Physiol. 27): H521-H528, 1990.-Acute plasma volume reduc- tion by atria1 natriuretic peptide (ANP) may be mediated, at least in part, by increased exchange vessel water conductivity (I,,). The present study tests the hypothesis that physiological levels of ANP acutely and reversibly elevate single capillary L,. Paired, in situ measurements of L, were obtained using the modified Landis technique in individually perfused mesenteric capillaries of the frog, Rana pipiens. Control L, measurements ranged from 0.1 to 40 x 10m7 cm. s-l cmHZO-’ (with a median value of 2.5 x lo-‘) in 81 microvessels perfused with frog Ringer solution containing dialyzed bovine serum albumin. Vessels were recannulated and perfused with one or more concentra- tions of human ANP (hANP) spanning the physiopathological range: 0.01, 0.1, 1, 10, and 100 nM. When possible, a final recannulation and L, determination was performed in the ab- sence of hANP. A median 2.2-fold rapid L, increase was ob- served compared with control at each peptide concentration. Lp changes persisted for the duration of exposure to hANP, returning to control levels on withdrawal of the peptide. True and venular capillaries exhibited similar L, responses: median 2% and U-fold elevations, respectively. Sixty percent of true and venular capillaries exhibited twofold or greater hANP- induced increases in IL,, whereas only 25% of arteriolar capil- laries exhibited such a response. Thus a differential sensitivity to the peptide exists across the exchange vessel network. The observations of this study demonstrate that physiological levels of ANP are capable of modulating exchange vessel L,, one means by which the peptide may acutely alter plasma volume. Furthermore, the presence of a response to basal levels of ANP suggests a maintenance role for the peptide in normal cardio- vascular volume homeostasis. frog mesentery; volume regulation; capillary permeability; hy- draulic conductance; single capillary ATRIAL NATRIURETIC PEPTIDE (ANP),a hormone ofcar- disc origin, is known to depress mean arterial pressure, plasma volume, and cardiac output (13, 20). The mech- anisms of action of the peptide to bring about these changes are still unresolved. With respect to the acute change in plasma volume, the diuretic and natriuretic actions of the peptide were initially considered of greatest importance (10). Recent observations, though, question the role of renal mechanisms mediating acute, ANP- induced plasma fluid shifts. Maack and co-workers (21) noted an increase in hematocrit despite replacement of urine output during ANP infusion in anesthetized dogs. Infusion of the peptide in healthy human volunteers was accompanied by a reversible intravascular volume con- traction not accounted for by renal fluid losses (3, 33). Furthermore, ANP infusion caused equivalent plasma volume reductions in nephrectomized and sham-operated rats (1, 12). Recently, Lee and Goldman (20) demon- strated a reduction in total blood volume primarily re- sponsible for the decrease in cardiac output of splenec- tomized dogs after ANP infusion. Together, these obser- vations suggest ANP-induced enhancement of nonrenal capillary filtration. Such an effect might result from altered Starling forces, filtration barrier, or capillary surface area. Huxley and co-workers (16) demonstrated a reversible increase in hydraulic conductivity (Lp) of single frog capillaries with luminal exposure to 10 ,uM ANP. Thus the peptide is able to directly alter the filtration barrier to water. Under resting conditions, mammalian plasma ANP ranges from 3 to 30 pM (13, 19). Release of the peptide under various physiological and pathological conditions may elevate circulating levels to several hundred pico- moles per liter (2,11,18). The present study was designed to investigate changes in single microvessel L, on expo- sure to ANP levels spanning the physiological and path- ophysiological range. An attempt was also made to dif- ferentiate peptide responses at different levels of the capillary network. Experiments were performed on frog mesenteric capillaries. Peptides homologous to mam- malian ANP have been identified in frog atrium and brain, suggesting similar functions in amphibians and mammals (25). The present study demonstrates a direct reversible elevation of single capillary &, with exposure to as low as 10 pM luminal human ANP (hANP). The greatest sensitivity to the peptide apparently resides in the mid to venular portions of the capillary network. METHODS Experimental preparation. All experiments were per- formed in situ on mesenteric microvessels of male North American leopard frogs (Rana pipiens, 6.5-7 cm body length, obtained from J.M. Hazen, VT). The frogs were housed in freshwater tanks at 1548°C and transferred to a holding tank at 20-24°C l-5 days before use. The animals were anesthetized by cerebral pith. Care was taken to leave the spinal cord intact. Cotton was placed within the cerebral cavity to ensure separation from the spinal cord. The animal was secured in the supine posi- tion, and the abdominal cavity exposed via a right lateral 0363-6135/90 $1.50 Copyright 0 1990 the American Physiological Society H521