May 1, 1989Open Access
Glomerular actions of endothelin in vivo.
Key Result
Endothelin infusion reduced single nephron glomerular filtration rate by 35% and glomerular plasma flow rate by 38% compared to non-exposed glomeruli.
Structured PICO
Does endothelin or antiendothelin antibody alter glomerular hemodynamics in Munich-Wistar rats?
P
Population
30 male Munich-Wistar rats weighing 180-230 g were studied to evaluate the in vivo effects of endothelin on renal cortical microcirculation.
I
Intervention
Infusion of human/porcine endothelin (0.4 ng/min) or antiendothelin antibody into a branch of the main renal artery
C
Comparator
Non-perfused glomeruli within the same kidney
O
Outcome
Single nephron glomerular filtration rate (SNGFR) and glomerular plasma flow ratesurrogate
Endothelin mediates significant renal vasoconstriction and hypofiltration, and its blockade ameliorates these effects in postischemic kidneys, suggesting a role in ischemic acute renal failure.
Main Result
Absolute Event Rate: 23.5% vs 35.9%
p-value: p=<0.005
Limitations
- The infusion pipette itself may alter hemodynamics by hindering blood flow
- Colloid-free and inulin-free infusate may confound calculations of SNGFR, filtration fraction, and glomerular plasma flow rate
Abstract
In Munich-Wistar rats, a micropipette was inserted into a first-order branch of the left main renal artery and continuously infused with human/porcine endothelin (0.4 ng/min). Micropuncture measurements revealed substantial differences within the cortical microcirculation of the same left kidney: SNGFR was some 35% lower in glomeruli exposed to endothelin compared with non-endothelin-perfused glomeruli (P less than 0.005). Similarly, glomerular plasma flow rate was some 38% lower in the endothelin-exposed glomeruli (P less than 0.001). The hypoperfusion and hypofiltration in the endothelin-exposed glomeruli reflected an increase in resistances in the afferent and efferent arterioles. There was no difference in the value of the glomerular capillary ultrafiltration coefficient between the two populations of glomeruli. We also studied kidneys that underwent 25 min of renal artery clamping 48 h before study. Antiendothelin antibody infused into one of the branches of the main renal artery ameliorated the vasoconstriction characteristic of postischemic nephrons: within the cortical microcirculation, the SNGFR in glomeruli exposed to antiendothelin antibody was 27.0 +/- 3.1 nl/min as compared with 17.4 +/- 1.7 measured in glomeruli not perfused with the antibody (P less than 0.001). Similarly, glomerular plasma flow rate was higher in the glomeruli exposed to antiendothelin antibody (128.7 +/- 14.4 nl/min vs. 66.6 +/- 5.6, P less than 0.005). Resistances in both the afferent and efferent arterioles were substantially lower in the antibody-exposed glomeruli. It is, therefore, suggested that endothelin, presumably released from damaged endothelium, may play an important intermediary role in the hypoperfusion and hypofiltration observed in postischemic kidneys.