Renal extraction and clearance of p‐aminohippurate during saline and dextrose infusion in the rat.

Abstract

SUMMARY1. The reliability of the use of p-aminohippurate (PAH) as a clearance marker for the determination of renal plasma flow during saline or dextrose infusion was investigated in conscious and anaesthetized rats.2. In the conscious rat (wt. 350-400 g) infused for 4 h with 0-85 % saline followed by 3 h of 2-5% dextrose, PAH clearance averaged 11-50 + 1-45 ml/min during saline infusion and 7-83 + 0-82 ml/min during dextrose infusion. The difference was significant (P < 0-02). Inulin clearance, however, was unchanged. With dextrose as the initial infusate, PAH clearance averaged 5-86 ± 0-65 ml/min and increased (P < 0-01) to 8-74 + 0-71 ml/min following a change of infusate to saline, although inulin clearance was again unchanged.3. In separate groups of rats anaesthetized with sodium pentobarbitone, a comparison was made between renal blood flow values calculated from PAH clearance and haematocrit, and those determined simultaneously using an electromagnetic flow probe placed on the left renal artery. During 0-85 % saline infusion, the calculated value was 88-1 + 8-4 % of that measured using the flow probe. During 2-5 % dextrose infusion the value determined from PAH clearance was only 47*3 + 4-2 % of that obtained using the flow probe, and this is significantly (P < 0-01) lower than the ratio found during saline infusion.4. In another study, renal venous blood samples were obtained from sodiumpentobarbitone-anaesthetized rats during 0-85 % saline or 2-5 % dextrose infusions, for calculation of the renal PAH extraction ratio. During saline infusion, PAH extraction averaged 68-3 + 2-5 %, whereas during dextrose infusion PAH extraction was lower (P < 0-001) and averaged only 48-8 + 3-2 %. It is concluded that PAH clearance grossly underestimates renal plasma flow during 2-5 % dextrose infusion in the rat.

Superiority of Tetraethylammonium to <i>p</i>-Aminohippurate as a Marker for Renal Plasma Flow during Furosemide Diuresis

“…probably due to inhibition of PAH secretion by endogenous products accumu lating in the uremic plasma [3,13,15]. Also the renal extraction of PAH has been shown to be decreased by glucose-water infusion [11] and by agents which increase renal blood flow (RBF) [1], Furosemide is an organic anion secreted by the same transtubular transport system as PAH in the proximal tubules [14], However, in previous studies little attention has been given to the possibility that the two sub stances could compete for the same transport system, although several investigations have used PAH clearance to estimate RPF during furosemide diuresis in humans [ 12, 2 1 ]. dogs [9,18,22], and cats [7], Only in one study [18] was RBF measured simultaneously by an electromagnetic flowmeter.…”

Tetraethylammonium and <i>ρ</i><i>-</i>Aminohippurate as Clearance Markers for Renal Plasma Flow in the Rat during Saline and Glucose Infusion

“…a fixed value for EpAn close to unity is often used, in order to circumvent the problem with sampling of renal venous blood. However, it has been shown in several studies that EPAH is not a constant pa rameter, but can be influenced by changes in renal blood flow [2], glomerular filtration rate [7], uremia [11], glucose infusion [9], and ad ministration of anionic drugs like furosemide [4], In an earlier study in conscious rats [13] we found that high doses of furosemide markedly decreased EPAH and CPAH. while the corre sponding values for tetraethylammonium (TEA), a compound transported by the orga nic cation system, were relatively unaffected.…”

“…The experiments were performed in anesthetized rats under normal 'control' conditions as well as during infusion of glucose, a condition known to depress EPA H [9]. For this purpose we have applied a newly developed experimental model using an an esthetized rat supplied with an extracorporeal circulation [14].…”

“…Provided that the rate of excretion equals the rate of extraction for such a compound, C will equal RPF, if the extraction fraction (E) is unity which is prob ably never the case [2,7,9,11]. Furthermore, for a given substance, E has no constant value, for which reason C and E should ideally be determined simultaneously in order to calcu late RPF as C/E [8].…”

Interactions Between Furosemide and the Renal Sympathetic Nerves

“…This effect has been observed even at low Li concentrations which are similar to plasma levels used in studies where Li is used as a clearance marker for proximal tubular Na transport (0.3 mM). Furthermore, EpAH de-creases during glucose infusion (Lote et al 1985;Rasmussen et al 1990), and during uremia (McNay et al 1976). Changes in RBF (Aukland & Lsyning 1970;Stein et al 1973) and filtration fraction (FF), (Haberle et al 1978) also influences EPAH.…”