Functional effects on glomerular hemodynamics of short-term chronic cyclosporine in male rats

J Clin Invest. 1989 Mar;83(3):960-9. doi: 10.1172/JCI113982.

Abstract

We evaluated the effects of chronic cyclosporine (CsA) administration on the determinants of nephron filtration rate (SNGFR) using micropuncture techniques (mp) in male Munich-Wistar rats. Animals received CsA (30 mg/kg SQ) in olive oil daily for 8 d before mp. Controls (PFC) were pair fed. SNGFR, glomerular capillary hydrostatic pressure gradient (delta P), nephron plasma flow (SNPF), plasma protein oncotic pressure (pi A), and glomerular ultrafiltration coefficient (LpA) were quantitated in each experiment. CsA was associated with a lower SNGFR due to decreases in SNPF and a major reduction in delta P but no decrease in LpA. Plasma volume expansion (PVE) caused SNGFR, delta P, and SNPF to increase in both CsA and PFC without eliminating the differences between CsA and PFC. CsA/PVE rats responded normally to angiotensin II (AII) infusion indicating that the low delta P associated with CsA is not due to unresponsiveness to AII. Prior renal denervation caused SNGFR and SNPF to increase in CsA-treated animals but failed to alter the reduction in glomerular capillary pressure after CsA or to eliminate the glomerular hemodynamic differences between treated animals and pair-fed controls. This constellation of glomerular hemodynamic abnormalities suggests that the renal effect of short-term chronic CsA administration is mediated primarily by a reduction in the afferent effective filtration pressure resulting from an imbalance between pre- and postglomerular vascular resistances.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiotensin II / pharmacology
  • Animals
  • Blood Proteins / metabolism
  • Capillaries / physiology
  • Cyclosporins / administration & dosage
  • Cyclosporins / pharmacology*
  • Denervation
  • Glomerular Filtration Rate / drug effects
  • Hemodynamics
  • Hydrostatic Pressure
  • Kidney / innervation
  • Kidney Glomerulus / blood supply
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / physiology*
  • Male
  • Nephrons / blood supply
  • Norepinephrine / metabolism
  • Plasma Volume
  • Rats
  • Regional Blood Flow
  • Vascular Resistance

Substances

  • Blood Proteins
  • Cyclosporins
  • Angiotensin II
  • Norepinephrine