Role of 20-hydroxyeicosatetraenoic acid in the renal and vasoconstrictor actions of angiotensin II

Q: What is the clinical evidence from this study?

Population: Hypertension / Angiotensin II pressor effects. Intervention: Angiotensin II and 20-HETE synthesis blockade (DDMS, ABT) vs. Baseline / Unblocked Angiotensin II response. Primary outcome: Mean arterial pressure (MAP) and 20-HETE formation.

Q: What does this research mean for the field?

Acute and chronic elevations in circulating angiotensin II stimulate renal 20-HETE formation, which contributes significantly to angiotensin II-induced renal vasoconstriction and pressor responses. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Magdalena Alonso‐Galicia; Kristopher G. Maier; Andrew S. Greene; Allen W. Cowley; Richard J. Roman

doi:10.1152/ajpregu.00664.2001

July 1, 2002AJP Regulatory Integrative and Comparative Physiology

Role of 20-hydroxyeicosatetraenoic acid in the renal and vasoconstrictor actions of angiotensin II

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Key result

20-HETE blockade blunts the angiotensin II-induced rise in mean arterial pressure by ~40%.

Key Points

To determine whether renal synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE) mediates the renal vasoconstrictor and pressor effects of acute and chronic angiotensin II exposure.
Evaluated diameter changes in isolated rat renal interlobular arteries exposed to angiotensin II before and after blocking 20-HETE synthesis with 17-octadecynoic acid.
Administered acute and 5-day continuous intravenous infusions of angiotensin II (50 ng·kg⁻¹·min⁻¹) to rats while assessing mean arterial pressure and 20-HETE levels with or without inhibitors DDMS and ABT.
Angiotensin II reduced interlobular artery diameter by 81 ± 8%, and 20-HETE synthesis blockade increased the ED50 15-fold while diminishing the maximal constrictor response by 61%.
Acute DDMS administration attenuated the 35 mmHg pressor response to graded angiotensin II by 40%, whereas 5-day angiotensin II infusion raised mean arterial pressure by 78 mmHg and cortical 20-HETE synthesis by 60%.
Chronic blockade of 20-HETE with DDMS or ABT attenuated the angiotensin II-driven rise in mean arterial pressure by 40% and blunted urinary 20-HETE excretion from 1,020 ± 105 ng/day down to 600 ± 25 and 400 ± 40 ng/day, respectively.

PICO

P

Population

Rats evaluated to determine the role of 20-HETE in the renal vasoconstrictor and pressor effects of angiotensin II.

I

Intervention / Comparator

Angiotensin II and 20-HETE synthesis blockade (DDMS, ABT) vs Baseline / Unblocked Angiotensin II response (Angiotensin II 5-200 ng/min or 50 ng/kg/min; DDMS 10 mg/kg or 1 mg/kg/h)

O

Primary Outcome

Mean arterial pressure (MAP) and 20-HETE formation

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Implication

Demonstrates that 20-HETE mediates renal vasoconstriction and blood pressure elevation induced by angiotensin II in rats, highlighting its role in acute and chronic hypertension.

Abstract

The present study examined the effects of ANG II on the renal synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE) and its contribution to the renal vasoconstrictor and the acute and chronic pressor effects of ANG II in rats. ANG II (10(-11) to 10(-7) mol/l) reduced the diameter of renal interlobular arteries treated with inhibitors of nitric oxide synthase and cyclooxygenase, lipoxygenase, and epoxygenase by 81 +/- 8%. Subsequent blockade of the synthesis of 20-HETE with 17-octadecynoic acid (1 micromol/l) increased the ED(50) for ANG II-induced constriction by a factor of 15 and diminished the maximal response by 61%. Graded intravenous infusion of ANG II (5-200 ng/min) dose dependently increased mean arterial pressure (MAP) in thiobutylbarbitol-anesthetized rats by 35 mmHg. Acute blockade of the formation of 20-HETE with dibromododecenyl methylsulfimide (DDMS; 10 mg/kg) attenuated the pressor response to ANG II by 40%. An intravenous infusion of ANG II (50 ng. kg(-1). min(-1)) in rats for 5 days increased the formation of 20-HETE and epoxyeicosatrienoic acids (EETs) in renal cortical microsomes by 60 and 400%, respectively, and increased MAP by 78 mmHg. Chronic blockade of the synthesis of 20-HETE with intravenous infusion of DDMS (1 mg. kg(-1). h(-1)) or EETs and 20-HETE with 1-aminobenzotriazole (ABT; 2.2 mg. kg(-1). h(-1)) attenuated the ANG II-induced rise in MAP by 40%. Control urinary excretion of 20-HETE averaged 350 +/- 23 ng/day and increased to 1,020 +/- 105 ng/day in rats infused with ANG II (50 ng. kg(-1). min(-1)) for 5 days. In contrast, urinary excretion of 20-HETE only rose to 400 +/- 40 and 600 +/- 25 ng/day in rats chronically treated with ANG II and ABT or DDMS respectively. These results suggest that acute and chronic elevations in circulating ANG II levels increase the formation of 20-HETE in the kidney and peripheral vasculature and that 20-HETE contributes to the acute and chronic pressor effects of ANG II.

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Cite This Study

Alonso‐Galicia et al. (2002) studied Hypertension / Angiotensin II pressor effects. Angiotensin II and 20-HETE synthesis blockade (DDMS, ABT) vs. Baseline / Unblocked Angiotensin II response was evaluated on Mean arterial pressure (MAP) and 20-HETE formation. Acute and chronic elevations in circulating angiotensin II increased renal 20-HETE formation, and 20-HETE blockade attenuated the angiotensin II-induced rise in mean arterial pressure by 40%.

synapsesocial.com/papers/6a6f213c5d37378ac1dc33e3 https://doi.org/10.1152/ajpregu.00664.2001

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Role of 20-hydroxyeicosatetraenoic acid in the renal and vasoconstrictor actions of angiotensin II

Key Points

PICO

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Implication

Abstract

Discussion

Cite This Study

Role of 20-hydroxyeicosatetraenoic acid in the renal and vasoconstrictor actions of angiotensin II

Key Points

PICO

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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