Transcytosis inhibitor N-ethylmaleimide increases microvascular permeability in rat muscle.
N-ethylmaleimide (NEM) has been claimed to markedly inhibit the transvascular passage of small proteins and albumin by interacting with the docking and fusion of plasmalemmal vesicles with their target membranes. To investigate the role of transcytosis in the transcapillary passage of albumin, we assessed the effects of NEM on (125)I-labeled radioiodinated serum albumin clearance (RISA-Cl) from blood to muscle in isolated and maximally vasodilated perfused rat hindquarters, in which vascular pressures, pre- and postcapillary resistances, and the capillary filtration coefficient (CFC) were continuously monitored. NEM (0.3-0.5 mM) caused a marked increase mainly in precapillary vascular resistance. Thus the arterial-to-venous resistance ratio in NEM-treated animals was 3.12 +/- 0.56 versus 1.66 +/- 0.17 during the control period (P < 0.05). Despite that, there was a doubling of both CFC from 0.0363 +/- 0.0028 to 0.0778 +/- 0.0101 ml x min(-1) x mmHg(-1) x 100 g(-1) (P < 0.01) and RISA-Cl, compared with the control situation, signaling markedly increased microvascular permeability. Our results strongly suggest that NEM, besides producing marked vasoconstriction, also causes damage to the capillary endothelium. Thus, instead of inhibiting transvascular transport, NEM may induce increases in the bulk transport of albumin from blood to tissue.
Carlsson
O
O
Department of Nephrology, Lund University, S-221 85 Lund, Sweden. Ola.Carlsson@gambro.com
Rosengren
B I
BI
Rippe
B
B
D000818:Animals; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects*; D005033:Ethylmaleimide / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D018482:Muscle, Skeletal / Q000098:blood supply*; D051381:Rats; D017208:Rats, Wistar; D012711:Serum Albumin, Radio-Iodinated / Q000493:pharmacokinetics; D014655:Vascular Resistance / Q000187:drug effects
D012711:Serum Albumin, Radio-Iodinated; D005033:Ethylmaleimide