Atrial natriuretic peptide modulation of albumin clearance and contrast agent permeability in mouse skeletal muscle and skin: role in regulation of plasma volume.
Atrial natriuretic peptide (ANP) via its guanylyl cyclase-A (GC-A) receptor participates in regulation of arterial blood pressure and vascular volume. Previous studies demonstrated that concerted renal diuretic/natriuretic and endothelial permeability effects of ANP cooperate in intravascular volume regulation. We show that the microvascular endothelial contribution to the hypovolaemic action of ANP can be measured by the magnitude of the ANP-induced increase in blood-to-tissue albumin transport, measured as plasma albumin clearance corrected for intravascular volume change, relative to the corresponding increase in ANP-induced renal water excretion. We used a two-tracer method with isotopically labelled albumin to measure clearances in skin and skeletal muscle of: (i) C57BL6 mice; (ii) mice with endothelium-restricted deletion of GC-A (floxed GC-A x tie2-Cre: endothelial cell (EC) GC-A knockout (KO)); and (iii) control littermates (floxed GC-A mice with normal GC-A expression levels). Comparison of albumin clearances in hypervolaemic EC GC-A KO mice with normovolaemic littermates demonstrated that skeletal muscle albumin clearance with ANP treatment accounts for at most 30% of whole body clearance required for ANP to regulate plasma volume. Skin microcirculation responded to ANP similarly. Measurements of permeability to a high molecular mass contrast agent (35 kD Gadomer) by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) enabled repeated measures in individual animals and confirmed small increases in muscle and skin microvascular permeability after ANP. These quantitative methods will enable further evaluation of the contribution of ANP-dependent microvascular beds (such as gastro-intestinal tract) to plasma volume regulation.
Curry
Fitz-Roy E
FR
Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, Davis, CA 95616, USA. fecurry@ucdavis.edu
Rygh
Cecilie Brekke
CB
Karlsen
Tine
T
Wiig
Helge
H
Adamson
Roger H
RH
Clark
Joyce F
JF
Lin
Yueh-Chen
YC
Gassner
Birgit
B
Thorsen
Frits
F
Moen
Ingrid
I
Tenstad
Olav
O
Kuhn
Michaela
M
Reed
Rolf K
RK
D000418:Albumins / Q000378:metabolism*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D005260:Female; D008279:Magnetic Resonance Imaging; D051379:Mice; D018345:Mice, Knockout; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D010953:Plasma Volume / Q000187:drug effects / Q000502:physiology*; D017461:Receptors, Atrial Natriuretic Factor / Q000502:physiology*; D012867:Skin / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
D000418:Albumins; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A