Unlike unmodified dissociable bovine hemoglobin (UHb), cross-linked hemoglo
bins do not dissociate into dimers, do not cross the glomerular filter, and
are retained in the plasma for a longer time. Renal peritubular capillarie
s, which are different from the glomerulus, allow the passage of molecules
as large as albumin into the renal interstitium. Cross-linked hemoglobins s
hould pass across these capillaries, enter the renal interstitium, and drai
n through the renal lymphatics. The present experiments were done in anesth
etized rats to determine the appearance of UHb, an intramolecularly cross-l
inked tetrameric hemoglobin (DECHb), and a polymerized bovine hemoglobin (P
Hb) of larger molecular size into the renal hilar lymph. Renal hilar lymph
samples were obtained before and after an isovolemic exchange of 2 mL/100 g
rat weight of a 6% solution of each hemoglobin for blood. The behavior of
a 5% solution of Evan's blue-labeled albumin was also determined for compar
ison. After exchange, the initial plasma concentration of each of the prote
ins was in excess of 20 mg/mL. UHb appeared both in urine and lymph. DECHb,
PHb, and albumin were absent from the urine but appeared promptly in the r
enal hilar lymph and reached concentrations at least 30% that of plasma. PH
b had a significantly smaller lymph clearance (in microliters per minute) a
nd longer plasma half-time than the other nondissociable proteins, These fi
ndings indicate that DECHb and PHb, although not filtered, pass across peri
tubular capillaries and readily enter the renal interstitial space, The pas
sage of the larger molecularsized PHb may be hindered relative to the other
proteins in passage across peritubular and other systemic capillaries.