ANP dependent regulation of vascular permeability and plasma volume in mice

Mice with endothelial‐restricted deletion of the guanylyl cyclase‐A (GC‐A) receptor for ANP (EC GC‐A KO) have expanded intravascular volumes, and reduced tissue albumin content with acute increases in plasma ANP (Sabrane et al. J Clin Invest 115:1666, 2005). To further test the hypothesis that ANP regulates plasma volume by modulating vascular permeability, we used pharmacological methods to modulate permeability, and measured blood to tissue albumin clearance in mouse models. Pretreatment of isoflurane‐anaesthetized mice with rolipram (8 mg/kg IP, 30 min) was used to stabilize the endothelial barrier in C57 black mice. Albumin clearances, measured using a dual label fluorescence method (FASEB J 20:A708), were: 24.6±5 and 13.8 ±1.3 (μl/g dry/30 min x10 4 , SEM) in skin and skeletal muscle respectively (n=18) in the presence of ANP alone (500 ng/kg/min), and 9.7±1.3 and 9.2±0.7 in skin and muscle in the presence of ANP with rolipram pretreatment (n=17). Fractional reductions in ANP/rolipram clearances were similar to those measured in preliminary results in EC GC‐A KO mice (dual isotope method). In KO as compared to control littermates, ANP‐stimulated albumin clearance was significantly reduced in skin (53%) (n=6) and there was a trend for reduced clearance in muscle (by 80%), trachea (75%) and heart (75%). Is albumin clearance attenuated in both KO and rolipram treated mice after acute plasma volume expansion?