Role of nitric oxide in the renal and systemic vasodilatory responses to platelet-activating factor in the rat, in vivo

Rajash K. Handa, Jack W. Strandhoy, Shelly E. Handa

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background/Aim: Chemical mediator(s) involved in the renal vasodilatory and systemic hypotensive effects of platelet-activating factor (PAF) remain unresolved. Because nitric oxide (NO) and PAF have many similar cardiovascular actions, we examined whether endogenous NO contributes to the renal and systemic actions of PAF. Methods: PAF was administered into the renal arterial or systemic venous circulation of anesthetized rats. The change in renal blood flow (RBF) and/or mean arterial blood pressure (MAP) was recorded in the absence and presence of NO synthase inhibition. Results: Transient exposure of the renal vacsular bed to intrarenal PAF boluses (1-10 ng kg-1) resulted in an immediate increase in RBF that was partially inhibited by the intrarenal administration of a NO synthase inhibitor, whereas the ensuing rapid fall in MAP was unaffected by NO synthase blockade. A sustained exposure to intrarenal PAF infusion (2.5 ng min-1 kg-1) in intrarenal NO synthase inhibitor-treated rats (hypertensive with vasoconstricted kidneys) had no effect on RBF and MAP, which was in contrast to the increase in RBF and modest fall in MAP in control intrarenal vasopressin-treated rats (hypertensive with vasoconstricted kidneys). To dissociate the influence of systemic hypotension on the RBF response, rat kidneys were denervated and MAP elevated by a pressor agent whilst maintaining renal arterial blood pressure constant. Subsequent intrarenal PAF infusion at 2.5 and 10 ng min-1 kg-1 resulted in a substantial rise in RBF and modest fall in MAP, responses that were abolished by intrarenal NO synthase inhibition at the lower intrarenal PAF infusion or abolished/attenuated at the higher intrarenal PAF infusion. Additional experiments administered drugs intravenously to exclude the possibility that the modified MAP response by NO synthase inhibition was related to the drugs being administered into the kidney. Intravenous PAF boluses (0.1-1 μg kg-1) resulted in a transient fall in MAP that was independent of the NO pathway, whereas the systemic hypotension induced by intravenous PAF infusion (10 ng min-1 kg-1) was greatly attenuated by NO synthase inhibition. Conclusion: NO has a major role in mediating the renal and peripheral vasodilatory responses induced by a sustained exposure to PAF in the rat, whereas NO's overall contribution was less or absent during transient PAF exposure.

Original languageEnglish (US)
Pages (from-to)165-175
Number of pages11
JournalKidney and Blood Pressure Research
Volume26
Issue number3
DOIs
StatePublished - Aug 11 2003

Fingerprint

Platelet Activating Factor
Arterial Pressure
Nitric Oxide
Kidney
Renal Circulation
Nitric Oxide Synthase
Controlled Hypotension
Vasopressins

Keywords

  • Blood flow
  • Blood pressure
  • Kidney
  • Nitric oxide
  • Platelet-activating factor
  • Rat

ASJC Scopus subject areas

  • Physiology
  • Nephrology
  • Cardiology and Cardiovascular Medicine

Cite this

Role of nitric oxide in the renal and systemic vasodilatory responses to platelet-activating factor in the rat, in vivo. / Handa, Rajash K.; Strandhoy, Jack W.; Handa, Shelly E.

In: Kidney and Blood Pressure Research, Vol. 26, No. 3, 11.08.2003, p. 165-175.

Research output: Contribution to journalArticle

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N2 - Background/Aim: Chemical mediator(s) involved in the renal vasodilatory and systemic hypotensive effects of platelet-activating factor (PAF) remain unresolved. Because nitric oxide (NO) and PAF have many similar cardiovascular actions, we examined whether endogenous NO contributes to the renal and systemic actions of PAF. Methods: PAF was administered into the renal arterial or systemic venous circulation of anesthetized rats. The change in renal blood flow (RBF) and/or mean arterial blood pressure (MAP) was recorded in the absence and presence of NO synthase inhibition. Results: Transient exposure of the renal vacsular bed to intrarenal PAF boluses (1-10 ng kg-1) resulted in an immediate increase in RBF that was partially inhibited by the intrarenal administration of a NO synthase inhibitor, whereas the ensuing rapid fall in MAP was unaffected by NO synthase blockade. A sustained exposure to intrarenal PAF infusion (2.5 ng min-1 kg-1) in intrarenal NO synthase inhibitor-treated rats (hypertensive with vasoconstricted kidneys) had no effect on RBF and MAP, which was in contrast to the increase in RBF and modest fall in MAP in control intrarenal vasopressin-treated rats (hypertensive with vasoconstricted kidneys). To dissociate the influence of systemic hypotension on the RBF response, rat kidneys were denervated and MAP elevated by a pressor agent whilst maintaining renal arterial blood pressure constant. Subsequent intrarenal PAF infusion at 2.5 and 10 ng min-1 kg-1 resulted in a substantial rise in RBF and modest fall in MAP, responses that were abolished by intrarenal NO synthase inhibition at the lower intrarenal PAF infusion or abolished/attenuated at the higher intrarenal PAF infusion. Additional experiments administered drugs intravenously to exclude the possibility that the modified MAP response by NO synthase inhibition was related to the drugs being administered into the kidney. Intravenous PAF boluses (0.1-1 μg kg-1) resulted in a transient fall in MAP that was independent of the NO pathway, whereas the systemic hypotension induced by intravenous PAF infusion (10 ng min-1 kg-1) was greatly attenuated by NO synthase inhibition. Conclusion: NO has a major role in mediating the renal and peripheral vasodilatory responses induced by a sustained exposure to PAF in the rat, whereas NO's overall contribution was less or absent during transient PAF exposure.

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KW - Blood flow

KW - Blood pressure

KW - Kidney

KW - Nitric oxide

KW - Platelet-activating factor

KW - Rat

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