Distinct role of nitric oxide and endothelium-derived hyperpolarizing factor in renal microcirculation. Studies in the isolated perfused hydronephrotic kidney

Nephron. 2002 Dec;92(4):905-13. doi: 10.1159/000065460.

Abstract

Background: Both nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) are established as important factors determining the vascular tone. The relative contribution of these factors to the renal microvascular tone, however, has not been delineated.

Methods: Isolated perfused hydronephrotic rat kidneys were used to characterize the relative role of NO and EDHF in mediating the tone of interlobular arteries (ILA) and afferent arterioles (AFF).

Results: During the norepinephrine constriction, acetylcholine (ACH, 1 micromol/l) induced a sustained vasodilation of ILA (90 +/- 9% reversal) and AFF (117 +/- 13% reversal). In the presence of nitro-L-arginine methylester (LNAME), the ACH-induced vasodilation of ILA and AFF was converted to transient dilation, with only 53 +/- 7 and 32 +/- 7% reversal observed 10 min after 1 micromol/l ACH (i.e sustained phase). In contrast, LNAME had no effect on the initial phase of ACH-induced dilation. In the presence of apamin + charybdotoxin, the initial vasodilator response to ACH (1 micromol/l) was diminished (ILA, from 108 +/- 8 to 46 +/- 9%; AFF, from 108 +/- 14 to 58 +/- 8%), whereas no impairment was observed in sustained phases. Furthermore, the magnitude of the vasoconstriction caused by LNAME was greater at smaller vessel segments. Finally, the LNAME-induced inhibition of the sustained phase of ACH-induced vasodilation was greater as the vessel diameter decreased.

Conclusions: That the relative contribution of NO and EDHF differs, with a greater role of NO in the basal tone and ACH-induced vasodilation at smaller vascular segments of ILA and AFF.

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Apamin / pharmacology
  • Arteries / drug effects
  • Arteries / metabolism
  • Biological Factors / metabolism*
  • Charybdotoxin / pharmacology
  • Endothelium, Vascular / metabolism
  • Enzyme Inhibitors / pharmacology
  • Hydronephrosis / metabolism
  • In Vitro Techniques
  • Kidney / blood supply*
  • Kidney / metabolism
  • Male
  • Microcirculation* / drug effects
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / metabolism*
  • Norepinephrine / pharmacology
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels / metabolism
  • Rats
  • Rats, Wistar
  • Vasoconstrictor Agents / pharmacology
  • Vasodilation / drug effects
  • Vasodilation / physiology
  • Vasodilator Agents / pharmacology

Substances

  • Biological Factors
  • Enzyme Inhibitors
  • Potassium Channel Blockers
  • Potassium Channels
  • Vasoconstrictor Agents
  • Vasodilator Agents
  • endothelium-dependent hyperpolarization factor
  • Charybdotoxin
  • Apamin
  • Nitric Oxide
  • Acetylcholine
  • NG-Nitroarginine Methyl Ester
  • Norepinephrine