Evidence for glomerular actions of epidermal growth factor in the rat

R. C. Harris, R. L. Hoover, H. R. Jacobson, K. F. Badr

Research output: Contribution to journalArticle

Abstract

Epidermal growth factor (EGF), an endogenous mitogenic peptide, has recently been shown to be a potent vasoconstrictor of vascular smooth muscle. In view of its potential role in proliferative and inflammatory renal glomerular diseases, we examined the effects of EGF both on cultured rat mesangial cells and on in vivo glomerular hemodynamics. Mesangial cells possess specific, saturable EGF receptors of differing affinities, with K(d)'s of 0.1 and 1.7 nM, respectively. EGF produced a rapid increase in intracellular pH of 0.12 ± 0.01 pH U, which was sodium dependent and amiloride inhibitable. The addition of EGF to mesangial cells cultured on either glass or dimethylpolysiloxane substratum induced reproducible cell contraction. Intrarenal EGF infusion did not affect systemic blood pressure or hematocrit but reversibly decreased GFR and renal blood flow from 4.19 ± 0.33 to 3.33 ± 0.26 and from 1.17 ± 0.09 to 0.69 ± 0.07 ml/min, respectively. Glomerular micropuncture confirmed decreases in single nephrone plasma flow and in single nephron GFR (from 142 ± 9 to 98 ± 8 and from 51.6 ± 11.7 to 28.5 ± 3.5 nl/min, respectively) which were due to significant increases in both pre- and postglomerular arteriolar resistances (from 1.97 ± 0.31 to 2.65 ± 0.36 and from 1.19 ± 0.11 to 2.00 ± 0.15 1010 dyn · s · cm-5 respectively) and to a significant decrease in the ultrafiltration coefficient, K(f), which fell from 0.100 ± 0.019 to 0.031 ± 0.007 nl/(s · mmHg). These studies demonstrate that mesangial cells possess specific receptors for EGF, and exposure of these cells to physiologic concentrations of EGF results in an in vitro functional response characterized by activation of Na+/H+ exchange and by resultant intracellular alkalinization, as well as by cell contraction. EGF administration in vivo significantly reduces the glomerular capillary ultrafiltration coefficient, K(f), which, in combination with EGF-induced constriction of both preglomerular and postglomerular arterioles, results in acute major reductions in the rates of glomerular filtration and perfusion.

Original languageEnglish (US)
Pages (from-to)1028-1039
Number of pages12
JournalJournal of Clinical Investigation
Volume82
Issue number3
StatePublished - 1988
Externally publishedYes

Fingerprint

Epidermal Growth Factor
Mesangial Cells
Ultrafiltration
Dimethylpolysiloxanes
Amiloride
Renal Circulation
Nephrons
Arterioles
Vasoconstrictor Agents
Glomerular Filtration Rate
Vascular Smooth Muscle
Hematocrit
Punctures
Constriction
Glass
Perfusion
Hemodynamics
Sodium
Blood Pressure
Kidney

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Harris, R. C., Hoover, R. L., Jacobson, H. R., & Badr, K. F. (1988). Evidence for glomerular actions of epidermal growth factor in the rat. Journal of Clinical Investigation, 82(3), 1028-1039.

Evidence for glomerular actions of epidermal growth factor in the rat. / Harris, R. C.; Hoover, R. L.; Jacobson, H. R.; Badr, K. F.

In: Journal of Clinical Investigation, Vol. 82, No. 3, 1988, p. 1028-1039.

Research output: Contribution to journalArticle

Harris, RC, Hoover, RL, Jacobson, HR & Badr, KF 1988, 'Evidence for glomerular actions of epidermal growth factor in the rat', Journal of Clinical Investigation, vol. 82, no. 3, pp. 1028-1039.
Harris RC, Hoover RL, Jacobson HR, Badr KF. Evidence for glomerular actions of epidermal growth factor in the rat. Journal of Clinical Investigation. 1988;82(3):1028-1039.
Harris, R. C. ; Hoover, R. L. ; Jacobson, H. R. ; Badr, K. F. / Evidence for glomerular actions of epidermal growth factor in the rat. In: Journal of Clinical Investigation. 1988 ; Vol. 82, No. 3. pp. 1028-1039.
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