Role of changes in renal hemodynamics and P-450 metabolites of arachidonic acid in the reversal of one-kidney, one clip hypertension

Ai Ping Zou, E. Eric Muirhead, Allen W. Cowley, David L. Mattson, John R. Falckt, Jian Jiang, Richard J. Roman

Research output: Contribution to journalArticle

Abstract

Objective: To examine the role of changes in renal hemodynamics and P-450 metabolites of arachidonic acid in the reversal of one-kidney, one clip (1-K, 1C) hypertension in rats. Design: The stimulus for the release of an antihypertensive lipid from the kidney is not known. This study examined whether cortical or papillary blood flow is altered after removal of the clip from the renal artery of 1 -K, 1 C hypertensive rats, and the effects of blockade of the renal metabolism of arachidonic acid by P-450 with 1 7-octadecynoic acid (17-ODYA) on the fall in blood pressure. Methods: Cortical and medullary blood flows were measured using laser-Doppler flowmetry. 17-ODYA (33nmol/min) was infused directly into the renal artery to examine the effect of inhibition of renal P-450 activity on reversal of 1-K, 1C hypertension. The renal metabolism of arachidonic acid in control and in 1-K, 1C hypertensive rats was assessed by incubating microsomes with [14C]-arachidonic acid, the metabolites formed being measured using reverse-phase high-performance liquid chromatography. The antihypertensive effects of these P-450 metabolites of arachidonic acid were compared with those of medullipin I after intravenous administration in conscious spontaneously hypertensive rats (SHR). Results: Cortical and papillary blood flow increased significantly and arterial pressure fell after unclipping the renal artery in the 1-K, 1C hypertensive rats. 17-ODYA prevented the fall in blood pressure after unclipping. The production of epoxy- and dihydroxy-eicosatrienoic acids was elevated in microsomes prepared from the renal cortex of the 1-K, 1C hypertensive rats. However, intravenous administration of these metabolites did not mimic the effect of medullipin I to lower arterial pressure in SHR. Conclusion: Elevations in renal cortical or papillary blood flow, or both, may stimulate the release of a P-450-derived antihypertensive lipid from the kidney after unclipping of the renal artery in 1-K, 1C hypertensive rats. However, it is unlikely that this substance is a P-450 metabolite of arachidonic acid.

Original languageEnglish (US)
Article number00012
Pages (from-to)557-566
Number of pages10
JournalJournal of hypertension
Volume13
Issue number5
DOIs
StatePublished - May 1995
Externally publishedYes

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Surgical Instruments
Arachidonic Acid
Hemodynamics
Hypertension
Kidney
Renal Artery
Antihypertensive Agents
Acids
Inbred SHR Rats
Microsomes
Intravenous Administration
Arterial Pressure
Blood Pressure
Lipids
Laser-Doppler Flowmetry
Reverse-Phase Chromatography
High Pressure Liquid Chromatography

Keywords

  • Arachidonic acid
  • Cytochrome P-450
  • Hypertension
  • One clip Goldblatt hypertensive rat
  • One-kidney
  • Renal blood flow
  • Renal medulla

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Zou, A. P., Muirhead, E. E., Cowley, A. W., Mattson, D. L., Falckt, J. R., Jiang, J., & Roman, R. J. (1995). Role of changes in renal hemodynamics and P-450 metabolites of arachidonic acid in the reversal of one-kidney, one clip hypertension. Journal of hypertension, 13(5), 557-566. [00012]. https://doi.org/10.1097/00004872-199505000-00012

Role of changes in renal hemodynamics and P-450 metabolites of arachidonic acid in the reversal of one-kidney, one clip hypertension. / Zou, Ai Ping; Muirhead, E. Eric; Cowley, Allen W.; Mattson, David L.; Falckt, John R.; Jiang, Jian; Roman, Richard J.

In: Journal of hypertension, Vol. 13, No. 5, 00012, 05.1995, p. 557-566.

Research output: Contribution to journalArticle

Zou, Ai Ping ; Muirhead, E. Eric ; Cowley, Allen W. ; Mattson, David L. ; Falckt, John R. ; Jiang, Jian ; Roman, Richard J. / Role of changes in renal hemodynamics and P-450 metabolites of arachidonic acid in the reversal of one-kidney, one clip hypertension. In: Journal of hypertension. 1995 ; Vol. 13, No. 5. pp. 557-566.
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abstract = "Objective: To examine the role of changes in renal hemodynamics and P-450 metabolites of arachidonic acid in the reversal of one-kidney, one clip (1-K, 1C) hypertension in rats. Design: The stimulus for the release of an antihypertensive lipid from the kidney is not known. This study examined whether cortical or papillary blood flow is altered after removal of the clip from the renal artery of 1 -K, 1 C hypertensive rats, and the effects of blockade of the renal metabolism of arachidonic acid by P-450 with 1 7-octadecynoic acid (17-ODYA) on the fall in blood pressure. Methods: Cortical and medullary blood flows were measured using laser-Doppler flowmetry. 17-ODYA (33nmol/min) was infused directly into the renal artery to examine the effect of inhibition of renal P-450 activity on reversal of 1-K, 1C hypertension. The renal metabolism of arachidonic acid in control and in 1-K, 1C hypertensive rats was assessed by incubating microsomes with [14C]-arachidonic acid, the metabolites formed being measured using reverse-phase high-performance liquid chromatography. The antihypertensive effects of these P-450 metabolites of arachidonic acid were compared with those of medullipin I after intravenous administration in conscious spontaneously hypertensive rats (SHR). Results: Cortical and papillary blood flow increased significantly and arterial pressure fell after unclipping the renal artery in the 1-K, 1C hypertensive rats. 17-ODYA prevented the fall in blood pressure after unclipping. The production of epoxy- and dihydroxy-eicosatrienoic acids was elevated in microsomes prepared from the renal cortex of the 1-K, 1C hypertensive rats. However, intravenous administration of these metabolites did not mimic the effect of medullipin I to lower arterial pressure in SHR. Conclusion: Elevations in renal cortical or papillary blood flow, or both, may stimulate the release of a P-450-derived antihypertensive lipid from the kidney after unclipping of the renal artery in 1-K, 1C hypertensive rats. However, it is unlikely that this substance is a P-450 metabolite of arachidonic acid.",
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AU - Zou, Ai Ping

AU - Muirhead, E. Eric

AU - Cowley, Allen W.

AU - Mattson, David L.

AU - Falckt, John R.

AU - Jiang, Jian

AU - Roman, Richard J.

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N2 - Objective: To examine the role of changes in renal hemodynamics and P-450 metabolites of arachidonic acid in the reversal of one-kidney, one clip (1-K, 1C) hypertension in rats. Design: The stimulus for the release of an antihypertensive lipid from the kidney is not known. This study examined whether cortical or papillary blood flow is altered after removal of the clip from the renal artery of 1 -K, 1 C hypertensive rats, and the effects of blockade of the renal metabolism of arachidonic acid by P-450 with 1 7-octadecynoic acid (17-ODYA) on the fall in blood pressure. Methods: Cortical and medullary blood flows were measured using laser-Doppler flowmetry. 17-ODYA (33nmol/min) was infused directly into the renal artery to examine the effect of inhibition of renal P-450 activity on reversal of 1-K, 1C hypertension. The renal metabolism of arachidonic acid in control and in 1-K, 1C hypertensive rats was assessed by incubating microsomes with [14C]-arachidonic acid, the metabolites formed being measured using reverse-phase high-performance liquid chromatography. The antihypertensive effects of these P-450 metabolites of arachidonic acid were compared with those of medullipin I after intravenous administration in conscious spontaneously hypertensive rats (SHR). Results: Cortical and papillary blood flow increased significantly and arterial pressure fell after unclipping the renal artery in the 1-K, 1C hypertensive rats. 17-ODYA prevented the fall in blood pressure after unclipping. The production of epoxy- and dihydroxy-eicosatrienoic acids was elevated in microsomes prepared from the renal cortex of the 1-K, 1C hypertensive rats. However, intravenous administration of these metabolites did not mimic the effect of medullipin I to lower arterial pressure in SHR. Conclusion: Elevations in renal cortical or papillary blood flow, or both, may stimulate the release of a P-450-derived antihypertensive lipid from the kidney after unclipping of the renal artery in 1-K, 1C hypertensive rats. However, it is unlikely that this substance is a P-450 metabolite of arachidonic acid.

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KW - Arachidonic acid

KW - Cytochrome P-450

KW - Hypertension

KW - One clip Goldblatt hypertensive rat

KW - One-kidney

KW - Renal blood flow

KW - Renal medulla

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