Nitro-oleic acid inhibits angiotensin II-induced hypertension
Open accessAbstract
Rationale: Nitro-oleic acid (OA-NO 2) is a bioactive, nitric-oxide derived fatty acid with physiologically relevant vasculoprotective properties in vivo. OA-NO 2 exerts cell signaling actions as a result of its strong electrophilic nature and mediates pleiotropic cell responses in the vasculature. Objective: The present study sought to investigate the protective role of OA-NO 2 in angiotensin (Ang) II–induced hypertension. Methods and Results: We show that systemic administration of OA-NO 2 results in a sustained reduction of Ang II–induced hypertension in mice and exerts a significant blood pressure lowering effect on preexisting hypertension established by Ang II infusion. OA-NO 2 significantly inhibits Ang II contractile response as compared to oleic acid (OA) in mesenteric vessels. The improved vasoconstriction is specific for the Ang II type 1 receptor (AT 1 R)-mediated signaling because vascular contraction by other G-protein–coupled receptors is not altered in response to OA-NO 2 treatment. From the mechanistic viewpoint, OA-NO 2 lowers Ang II–induced hypertension independently of peroxisome proliferation-activated receptor (PPAR)γ activation. Rather, OA-NO 2, but not OA, specifically binds to the AT 1 R, reduces heterotrimeric G-protein coupling, and inhibits IP 3(inositol-1,4,5-trisphosphate) and calcium mobilization, without inhibiting Ang II binding to the receptor. Conclusions: These results demonstrate that OA-NO 2 diminishes the pressor response to Ang II and inhibits AT 1 R-dependent vasoconstriction, revealing OA-NO 2 as a novel antagonist of Ang II–induced hypertension.
AI snapshot
Written from the paper’s full text.
TL;DR
Nitro-oleic acid (OA-NO2) lowers angiotensin II (Ang II)-induced hypertension and preexisting hypertension in mice, while its non-nitrated counterpart oleic acid does not. Mechanistically, OA-NO2 adducts the AT1R without blocking Ang II binding, uncouples G-protein signaling, and inhibits downstream IP3 and calcium mobilization.
Key findings
- Systemic OA-NO2 (5 mg/kg/day) reduced Ang II-induced increases in systolic BP by ~15 mmHg and diastolic BP by ~12 mmHg compared with OA or vehicle, without apparent heart-rate changes.
- In isolated rat mesenteric vessels, OA-NO2 at 2.5 μmol/L produced ~50% reduction of Ang II-mediated vasoconstriction at 10−7 mol/L, and 5 μmol/L almost completely abolished Ang II contraction; responses to phenylephrine and endothelin-1 were not affected.
- OA-NO2 lowered Ang II-induced hypertension independently of PPARγ: GW9662 did not reverse the effect, and OA-NO2 persistently reduced Ang II-mediated BP elevation by ~10 mmHg with or without GW9662, whereas rosiglitazone’s ~7 mmHg BP reduction was antagonized by GW9662.
- OA-NO2 bound AT1R with a ~20-fold increase of adducted OA-NO2 in AT1R-expressing cells versus controls, did not interfere with Ang II binding, reduced AT1R–Gαq11 coupling, and inhibited Ang II-induced IP3 and calcium mobilization; 2.5 μmol/L OA-NO2 reduced the fura-2 ratio induced by Ang II by 75%, while 1 μmol/L losartan completely inhibited it.
Methods
- Mice were implanted with osmotic minipumps for OA-NO2 or OA at 5 mg/kg/day and Ang II at 500 ng/kg/min; BP was measured by radiotelemetry and by in vivo carotid catheter tracing, with jugular vein delivery of OA/OA-NO2 and the PPARγ inhibitor GW9662.
- Second-order rat mesenteric arteries were mounted on a myograph, pretreated with OA-NO2 or OA at 2.5 and 5 μmol/L, then contracted with Ang II, phenylephrine, or endothelin-1.
- AT1R binding/adduction was assessed in HEK293 cells overexpressing AT1R using trans-alkylation and HPLC-MS/MS, biotin-labeled OA-NO2 immunoprecipitation, Gαq11 coupling assays, IP3 measurement, and fura-2 calcium imaging.
Limitations
- The paper states that mechanisms underlying nitrated lipid production, structural isomer distributions, the nitrated fatty acid-susceptible proteome, and detailed signaling actions remain incompletely characterized.
- The paper states that Ang II infusion did not significantly change free nitroalkenes in plasma (data not shown) and that local generation of nitrated fatty acids within the vasculature in response to Ang II cannot be excluded.
- The paper states that further studies, including biochemical and crystallographic approaches, are needed to dissect how electrophilic fatty acid derivatives reduce Ang II-mediated hypertension; evident from the text, the mechanistic work relies heavily on HEK293 overexpression systems and ex vivo rodent vessels, with no human data reported.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
0 of 12 cited sources checked · 0 supported · 0 flagged
- Findingown data
OA-NO2 treatment does not alter heart rate in mice during Ang II infusion.
“without any apparent changes in the heart rate (Online Figure I).”
Quote in the paperNot a substantial claim - Findingown data
Inhibition of PPARγ by GW9662 does not attenuate Ang II-induced blood pressure increases.
“Moreover, GW9662 administration (10 mg/kg) compared to vehicle treated mice at the same infusion rate did not attenuate BP increases after Ang II challenge (Figure 4 and Online Figure II).”
Quote in the paperSubstantial claim - Findingown data
OA-NO2 lowers blood pressure in preexisting Ang II-induced hypertension when administered after Ang II infusion.
“We show that systemic administration of OA-NO2 results in a sustained reduction of Ang II-induced hypertension in mice and exerts a significant blood pressure lowering effect on preexisting hypertension established by Ang II infusion.”
- Also stated in: § OA-NO2 reduces Ang II-induced hypertension · plain
“Under these experimental conditions, OA-NO2 but not OA results in a dose-dependent reduction of BP to the preexisting Ang II-induced hypertension (Figure 2F).”
- Also stated in: § Discussion · boosted
“In summary, this is the first demonstration that OA-NO2 has a long-lasting impact on hypertension induced by Ang II infusion and exerts a significant BP lowering effect on preexisting hypertension.”
Quote in the paperSubstantial claim - Also stated in: § OA-NO2 reduces Ang II-induced hypertension · plain
- Findingown data
OA-NO2 inhibits Ang II-induced IP3 and calcium mobilization downstream of AT1R.
“inhibits IP3 and calcium mobilization”
- Also stated in: § OA-NO2 interferes with G-protein coupling to the AT1R and prevents Ang II-mediated contractile responses in vascular smooth muscle cells (VSMC) · plain
“Competitive radioreceptor analysis showed that OA-NO2, but not OA, reduced Ang II-induced intracellular inositol-1,4,5-trisphosphate (IP3) mobilization (Figure 6C).”
- Also stated in: § OA-NO2 interferes with G-protein coupling to the AT1R and prevents Ang II-mediated contractile responses in vascular smooth muscle cells (VSMC) · plain
“Accordingly, we show a dose-dependent inhibition of Ang II-mediated increase in intracellular calcium mobilization ([Ca2+]i) upon OA-NO2 treatment, as determined by fluorescence imaging of fura-2 (Figure 6D).”
Quote in the paperSubstantial claim - Also stated in: § OA-NO2 interferes with G-protein coupling to the AT1R and prevents Ang II-mediated contractile responses in vascular smooth muscle cells (VSMC) · plain
- Findingown data
OA-NO2 reduces Ang II-dependent vasoconstriction with or without PPARγ antagonism by GW9662.
“As shown in Figure 4D, OA-NO2 similarly diminished Ang II-dependent vasoconstriction with or without PPARγ antagonism by GW9662 treatment.”
Quote in the paperSubstantial claim
- Findingown data
OA-NO2 reduces heterotrimeric G-protein coupling to the AT1R.
“reduces heterotrimeric G-protein coupling”
- Also stated in: § OA-NO2 interferes with G-protein coupling to the AT1R and prevents Ang II-mediated contractile responses in vascular smooth muscle cells (VSMC) · plain
“OA-NO2 but not OA significantly reduced AT1R coupled to the immunoprecipitated Gαq11 after 1 min stimuli with Ang II (100 nmol/L) (Figure 6A and 6B).”
- Also stated in: § What New Information Does This Article Contribute? · plain
“OA-NO2 reduces heterotrimeric G-protein coupling to the AT1R and inhibits downstream signaling.”
Quote in the paperSubstantial claim - Also stated in: § OA-NO2 interferes with G-protein coupling to the AT1R and prevents Ang II-mediated contractile responses in vascular smooth muscle cells (VSMC) · plain
- Findingown data
OA alone at the dosage used (5 mg/kg/day) does not reduce Ang II-mediated hypertension.
“Thus, at an infusion rate of 5mg/kg/day, reduction of Ang II-mediated hypertension is afforded by the nitrated but not free form of OA.”
- Also stated in: § Discussion · hedged
“Furthermore, comparative analysis with the inclusion of the OA-treated group, as the non-nitrated counterpart for OA-NO2 also indicates that OA alone at the dosage used in the present study did not reduce Ang II-mediated hypertension in contrast to previous studies indicating that OA or related species might be hypotensive37.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · hedged
- Findingown data
OA-NO2 lowers Ang II-induced hypertension independently of PPARγ activation.
“From the mechanistic viewpoint, OA-NO2 lowers Ang II-induced hypertension independently of peroxisome proliferation-activated receptor-γ (PPARγ) activation.”
- Also stated in: § OA-NO2 reduction of Ang II-induced hypertension is a PPARγ independent phenomenon · hedged
“This series of experiments indicate that PPARγ activation by OA-NO2 is not the major mechanism involved in OA-NO2 antagonism of both Ang II-mediated hypertension and vasoconstriction.”
- Also stated in: § Discussion · boosted
“Taking into account that OA-NO2 specifically reduced Ang II-mediated vascular contractility but did not interfere with the contractile properties of ET-1 and PE, it can be concluded that PPARγ activation by OA-NO2 is not the major mechanism involved in OA-NO2 effects on AngII-induced hypertension.”
Quote in the paperSubstantial claim - Also stated in: § OA-NO2 reduction of Ang II-induced hypertension is a PPARγ independent phenomenon · hedged
- Findingown data
OA-NO2 does not inhibit Ang II binding to the AT1R.
“without inhibiting Ang II binding to the receptor.”
- Also stated in: § OA-NO2 does not interfere with Ang II binding to the receptor · plain
“Unlike the ARB losartan, that inhibits Ang II binding to AT1R, neither OA-NO2 nor OA affected binding of radio-labeled Ang II to its receptor (Figure 5E).”
- Also stated in: § Discussion · hedged
“However, adduction of the AT1R by OA-NO2 did not interfere with Ang II binding to its receptor, suggesting that the molecular interactions between OA-NO2 and AT1R are unlikely similar to typical competitive inhibitors of AT1R44, 45.”
Quote in the paperSubstantial claim - Also stated in: § OA-NO2 does not interfere with Ang II binding to the receptor · plain
- Premisecitation
OA-NO2 exerts vasorelaxation of preconstricted aortic rings.
“In the context of the vasculature, OA-NO2 inhibits neointimal hyperplasia19 and exerts vasorelaxation of preconstricted aortic rings20.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [20] Lim DG Sweeney S Bloodsworth A White CR Chumley PH Krishna NR Schopfer F O’Donnell VB Eiserich JP Freeman BA Nitrolinoleate, a nitric oxide-derived mediator of cell function: synthesis, characterization, and vasomotor activity Proc Natl Acad Sci U S A 2002 99 15941 15946 12444258 PMC138544 source
Not checked in the free run.
- Premisecitation
Deregulation of Ang II production plays a critical role in the pathogenesis of hypertension.
“As the major component of the renin-angiotensin-aldosterone system, deregulation of Ang II production plays a critical role in the pathogenesis of hypertension22.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [22] Mehta PK Griendling KK Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system Am J Physiol Cell Physiol 2007 292 C82 97 16870827 source
Not checked in the free run.
- Interpretationown data
OA-NO2 diminishes the pressor response to Ang II in vivo regardless of whether it is administered before or after Ang II challenge.
“Taken together, these results demonstrate that OA-NO2 diminishes the pressor response to Ang II in vivo, regardless of whether the nitroalkene is administered before of after Ang II challenge.”
- Also stated in: § Discussion · boosted
“Thus, our long-term radiotelemetry analysis confirmed that OA-NO2 diminished the pressor response to Ang II rather than simply delay Ang II dependent hypertension.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · boosted
- Premisecitation
OA-NO2 activates PPARγ.
“For instance, nitro derivatives of linoleic and oleic (OA-NO2) acids are activators of peroxisome proliferator-activated receptor-γ (PPARγ)14, 15”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [14] Schopfer FJ Lin Y Baker PR Cui T Garcia-Barrio M Zhang J Chen K Chen YE Freeman BA Nitrolinoleic acid: an endogenous peroxisome proliferator-activated receptor gamma ligand Proc Natl Acad Sci U S A 2005 102 2340 2345 15701701 PMC548962 source
Not checked in the free run.
- cites [15] Li Y Zhang J Schopfer FJ Martynowski D Garcia-Barrio MT Kovach A Suino-Powell K Baker PR Freeman BA Chen YE Xu HE Molecular recognition of nitrated fatty acids by PPAR gamma Nat Struct Mol Biol 2008 15 865 867 18604218 PMC2538624 source
Not checked in the free run.
- Interpretationown data
OA-NO2 and rosiglitazone reduce established hypertension through different pathways.
“OA-NO2 and rosiglitazone reduce established hypertension through different pathways.”
- Also stated in: § OA-NO2 reduction of Ang II-induced hypertension is a PPARγ independent phenomenon · plain
“In response to rosiglitazone treatment, BP reduction (~7mmHg) was efficiently antagonized by GW9662 (Online Figure II), whereas OA-NO2 delivery in the presence of GW9662 results in a dose-dependent BP reduction comparable to the lack of the PPARγ antagonist (Online Figure III).”
Quote in the paperSubstantial claim - Also stated in: § OA-NO2 reduction of Ang II-induced hypertension is a PPARγ independent phenomenon · plain
- Premisecitation
Nitroalkenes transduce signaling reactions by covalently modifying nucleophilic protein targets and altering their structure and function.
“Nitroalkenes transduce signaling reactions by covalently modifying nucleophilic protein targets and altering their structure and function6.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [6] Freeman BA Baker PR Schopfer FJ Woodcock SR Napolitano A d’Ischia M Nitro-fatty acid formation and signaling J Biol Chem 2008 283 15515 15519 18285326 PMC2414282 source
Not checked in the free run.
- May combine two claims. 5
- The quote only partly states this claim. 2
- Classified as probably not a substantial claim. 3
May combine two claims. The quote only partly states this claim.
Findingown dataOA-NO2, but not OA, specifically binds to the AT1R, forming covalent adducts.
“Rather, OA-NO2, but not OA, specifically binds to the AT1R, reduces heterotrimeric G-protein coupling and inhibits IP3 and calcium mobilization, without inhibiting Ang II binding to the receptor.”
- Also stated in: § OA-NO2 forms covalent adducts with the AT1R receptor · boosted
“Thus, two independent approaches showed that AT1R is a relevant cellular target of OA-NO2 alkylation.”
- Also stated in: § Discussion · boosted
“Notably, we demonstrate by two independent experimental approaches that OA-NO2 binds to the AT1R.”
Quote in the paperSubstantial claim- Also stated in: § OA-NO2 forms covalent adducts with the AT1R receptor · boosted
The quote only partly states this claim.
Findingown dataOA-NO2 inhibits Ang II-induced vasoconstriction in isolated mesenteric vessels in a dose-dependent manner, compared to OA.
“OA-NO2 significantly inhibits Ang II contractile response as compared to oleic acid (OA) in mesenteric vessels.”
- Also stated in: § OA-NO2 specifically inhibits Ang II-induced vasoconstriction · plain
“Thus, OA-NO2 treatment dose-dependently reduced Ang II-dependent vasoconstriction.”
- Also stated in: § Discussion · plain
“In ex vivo vasoconstriction assays, OA-NO2 inhibited Ang II-mediated vascular contractility in an AT1R-dependent fashion.”
Quote in the paperSubstantial claim- Also stated in: § OA-NO2 specifically inhibits Ang II-induced vasoconstriction · plain
May combine two claims.
Findingown dataOA-NO2 treatment does not affect baseline systolic or diastolic blood pressure in mice.
“Systemic delivery of OA and OA-NO2 did not affect baseline systolic or diastolic BP recordings measured by radiotelemetry during the first week of the analysis as compared with polyethylenglycol-treated group that served as vehicle control (Figure 1A and 1C).”
- Also stated in: § OA-NO2 reduces Ang II-induced hypertension · plain
“OA and OA-NO2 (1 mmol/L, infusion rate: 1 μL/min) administered before Ang II delivery (1μmol/L, infusion rate: 1μL/min) did not alter basal BP recordings (Figure 2A and 2B).”
Quote in the paperSubstantial claim- Also stated in: § OA-NO2 reduces Ang II-induced hypertension · plain
May combine two claims.
Findingown dataSystemic administration of OA-NO2 (5 mg/kg/day) reduces Ang II-induced hypertension in mice, with sustained reduction of systolic (~15 mmHg) and diastolic (~12 mmHg) blood pressure compared to OA or vehicle.
“We show that systemic administration of OA-NO2 results in a sustained reduction of Ang II-induced hypertension in mice and exerts a significant blood pressure lowering effect on preexisting hypertension established by Ang II infusion.”
- Also stated in: § OA-NO2 reduces Ang II-induced hypertension · plain
“Under these conditions, OA-NO2 but not OA significantly reduced Ang II-dependent increases in systolic (~15 mmHg reduction) and diastolic BP (~12 mmHg reduction) compared to control OA or vehicle treated animals”
- Also stated in: § Discussion · plain
“Systemic delivery of pharmacological doses of OA-NO2 but not OA resulted in a prolonged and sustained reduction of BP throughout the 14 days of Ang II infusion.”
Quote in the paperSubstantial claim- Also stated in: § OA-NO2 reduces Ang II-induced hypertension · plain
May combine two claims.
Findingown dataOA-NO2's inhibition of vasoconstriction is specific for AT1R-mediated signaling, as contraction induced by other GPCR agonists (phenylephrine and endothelin-1) is not altered.
“The improved vasoconstriction is specific for the Ang II receptor (AT1R)-mediated signaling since vascular contraction by other G-protein coupled receptors is not altered in response to OA-NO2 treatment.”
- Also stated in: § OA-NO2 specifically inhibits Ang II-induced vasoconstriction · plain
“Interestingly, vasoconstriction elicited by signaling through other members of the G-protein coupled receptor family (GPCR), such as by treatment with phenylephrine (PE) and endothelin-1 (ET-1), was not affected upon OA-NO2 treatment at any concentration given (Figure 3B and 3C and Online Figure IV).”
- Also stated in: § Discussion · plain
“Specificity for the AT1R relies on the observations that OA-NO2 dose-dependently inhibited Ang II-mediated vessel contraction but did not reduced vascular contractility induced by vasoconstrictors signaling through other GPCR, such as the observed endothelin-1 and phenylephrine.”
Quote in the paperSubstantial claim- Also stated in: § OA-NO2 specifically inhibits Ang II-induced vasoconstriction · plain
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationOA-NO2 inhibits neointimal hyperplasia.
“In the context of the vasculature, OA-NO2 inhibits neointimal hyperplasia19 and exerts vasorelaxation of preconstricted aortic rings20.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [19] Cole MP Rudolph TK Khoo NK Motanya UN Golin-Bisello F Wertz JW Schopfer FJ Rudolph V Woodcock SR Bolisetty S Ali MS Zhang J Chen YE Agarwal A Freeman BA Bauer PM Nitro-fatty acid inhibition of neointima formation after endoluminal vessel injury Circ Res 2009 105 965 972 19797175 PMC2784279 source
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationPPARγ activators downregulate AT1R in vascular cells.
“PPARγ activators downregulate AT1R in vascular cells26, 27”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [26] Takeda K Ichiki T Tokunou T Funakoshi Y Iino N Hirano K Kanaide H Takeshita A Peroxisome proliferator-activated receptor gamma activators downregulate angiotensin II type 1 receptor in vascular smooth muscle cells Circulation 2000 102 1834 1839 11023940
Not checked in the free run.
- cites [27] Sugawara A Takeuchi K Uruno A Ikeda Y Arima S Kudo M Sato K Taniyama Y Ito S Transcriptional suppression of type 1 angiotensin II receptor gene expression by peroxisome proliferator-activated receptor-gamma in vascular smooth muscle cells Endocrinology 2001 142 3125 3134 11416035
Not checked in the free run.
May combine two claims.
Interpretationown dataOA-NO2 is a novel antagonist of Ang II-induced hypertension, acting via a mechanism distinct from competitive ARBs.
“These results demonstrate that OA-NO2 diminishes the pressor response to Ang II and inhibits AT1R-dependent vasoconstriction, revealing OA-NO2 as a novel antagonist of Ang II-induced hypertension.”
- Also stated in: § OA-NO2 does not interfere with Ang II binding to the receptor · hedged
“This indicates that OA-NO2 adduction of the AT1R does not affect Ang II binding and represents a novel manner of AT1R antagonism that is distinct from competitive ARBs31.”
- Also stated in: § Discussion · plain
“OA-NO2 antagonizes Ang II signaling due to the formation of stable adducts with the AT1R leading to a reduced vasoconstriction via uncoupling G-protein signaling and subsequently reducing second messenger mobilization.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [31] Vauquelin G Van Liefde I Vanderheyden P Models and methods for studying insurmountable antagonism Trends Pharmacol Sci 2002 23 514 518 12413806
Not checked in the free run.
- Also stated in: § OA-NO2 does not interfere with Ang II binding to the receptor · hedged
Classified as probably not a substantial claim.
PremisecitationCertain ARBs inhibit AT1R through PPARγ activity.
“certain ARBs inhibit AT1R through PPARγ activity28–30”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [28] Benson SC Pershadsingh HA Ho CI Chittiboyina A Desai P Pravenec M Qi N Wang J Avery MA Kurtz TW Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPARgamma-modulating activity Hypertension 2004 43 993 1002 15007034
Not checked in the free run.
- cites [29] Schupp M Janke J Clasen R Unger T Kintscher U Angiotensin type 1 receptor blockers induce peroxisome proliferator-activated receptor-gamma activity Circulation 2004 109 2054 2057 15117841
Not checked in the free run.
- cites [30] Imayama I Ichiki T Inanaga K Ohtsubo H Fukuyama K Ono H Hashiguchi Y Sunagawa K Telmisartan downregulates angiotensin II type 1 receptor through activation of peroxisome proliferator-activated receptor gamma Cardiovasc Res 2006 72 184 190 16938288
Not checked in the free run.
Claims other papers make about this one
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NO2-FA display signaling actions that expand both the pharmacokinetics and scope of nitric oxide (·NO) signaling events to include actions beyond the activation of guanylate cyclase-dependent cGMP production.
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Self-citationNrf2-dependent and -independent Responses to Nitro-fatty Acids in Human Endothelial Cells
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Self-citationMolecular Mechanism Underlying Inverse Agonist of Angiotensin II Type 1 Receptor
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Self-citationNitro-fatty Acid Metabolome: Saturation, Desaturation, β-Oxidation, and Protein Adduction
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Self-citationInterference With PPARγ Signaling Causes Cerebral Vascular Dysfunction, Hypertrophy, and Remodeling
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Self-citationModels and methods for studying insurmountable antagonism
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Self-citationOlives and olive oil are sources of electrophilic fatty acid nitroalkenes
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Self-citationCentral and Peripheral Irisin Differentially Regulate Blood Pressure
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Self-citationNitro-Fatty Acids: Formation, Redox Signaling, and Therapeutic Potential
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Self-citationLeptin‐Induced Endothelial Dysfunction Is Mediated by Sympathetic Nervous System Activity
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Self-citationAntihypertensive mechanism of lactoferrin-derived peptides: angiotensin receptor blocking effect.
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Self-citationElectrophilic nitro-oleic acid reverses obesity-induced hepatic steatosis
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Self-citationNitroalkylation — A redox sensitive signaling pathway
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Post-Translational Modification of Proteins Mediated by Nitro-Fatty Acids in Plants: Nitroalkylation
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Combined losartan and nitro-oleic acid remarkably improves diabetic nephropathy in mice
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Hypothesis: Nitro-fatty acids play a role in plant metabolism
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Self-citationNitrated fatty acids: from diet to disease
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Self-citationRecent Advances on Mass Spectrometry Analysis of Nitrated Phospholipids
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Nitro-oleic acid-mediated blood-brain barrier protection reduces ischemic brain injury
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Virgin Olive Oil and Hypertension
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New Insights into the Anti‐Inflammatory and Antioxidant Properties of Nitrated Phospholipids
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Self-citationNitro-Oleic Acid Regulates Endothelin Signaling in Human Endothelial Cells
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Fatty acid nitroalkene reversal of established lung fibrosis
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Peroxynitrite: Toxic Agent and Signaling Molecule (Review)
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Regulation of Angiotensin II receptor signaling by cysteine modification of NF-κB
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Nitrooleic Acid Protects against Cisplatin Nephropathy: Role of COX‐2/mPGES‐1/PGE2 Cascade
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Electrophilic nitro-fatty acids suppress allergic contact dermatitis in mice
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- Authors
- Zhang, J., Villacorta, L., Chang, L., Fan, Z., Hamblin, M., Zhu, T., Chen, C. S., Cole, M. P., Schopfer, F. J., Deng, C. X., Garcia-Barrio, M. T., Feng, Y.-H., Freeman, B. A., & Chen, Y. E.
- Affiliations
- Uniformed Services University of the Health Sciences (US)
- From the Cardiovascular Center (J.Z., L.V., L.C., M.H., T.Z., Y.E.C.); and Department of Biomedical Engineering (Z.F., C.X.D.), College of Engineering, University of Michigan; Department of Pharmacology & Chemical Biology (C.S.C., M.P.C., F.J.S., B.A.F.), University of Pittsburgh, Pa; Cardiovascular Research Institute (M.T.G.-B.), Morehouse School of Medicine, Atlanta, Ga; and Department of Pharmacology (Y.-H.F.), Uniformed Services University of the Health Sciences, Bethesda, Md.
- ORCID
- Venue
- Circulation Research
- Published
- 2010-08-20
- Volume
- 107
- Issue
- 4
- Pages
- 540-548
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- PMC
- PMC2937264
- OpenAlex
- W2097005377
- Semantic Scholar
- 1f60e0cb01c7a55c29e7b450dd3191e32d6cffcf
- Cited by
- 121
- References
- 50
- Citations by year
- 2025: 3 · 2024: 7 · 2023: 8 · 2022: 4 · 2021: 6 · 2020: 6 · 2019: 11 · 2018: 14 · 2017: 7 · 2016: 9 · 2015: 10 · 2014: 10 · 2013: 13 · 2012: 7
- FWCI
- 5.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL 64937, R01HL064937, HL 58115, R01HL089544, R37HL058115, R01HL058115, HL68878, R01HL088391, R01HL105114, R01HL068878, K99HL095769, R01HL075397, HL089544)
- National Cancer Institute (R01CA116592, CA116592)
- National Institute of Biomedical Imaging and Bioengineering (R01EB008999)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- nitro-oleic acid, angiotensin II, hypertension, angiotensin II type 1 receptor, vasoconstriction, G protein coupling, inositol trisphosphate, calcium mobilization, vascular protection, oleic acid
- MeSH terms
- Angiotensin II, Animals, Blood Pressure, Hypertension, Linoleic Acids, Mice, Inbred C57BL, Nitro Compounds, Oleic Acids, Rats, Sprague-Dawley, Oleic Acid, Mice, Rats
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