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Angiotensin converting enzyme inhibitors enhance the hypotensive effects of propofol by increasing nitric oxide production

Published on Feb 1, 2018in Free Radical Biology and Medicine5.66
· DOI :10.1016/j.freeradbiomed.2017.11.010
Gustavo H. Oliveira-Paula9
Estimated H-index: 9
(USP: University of São Paulo),
Lucas C. Pinheiro11
Estimated H-index: 11
(USP: University of São Paulo)
+ 4 AuthorsJosé Eduardo Tanus-Santos27
Estimated H-index: 27
(USP: University of São Paulo)
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Abstract
Abstract Propofol anesthesia is usually accompanied by hypotension. Studies have shown that the hypotensive effects of propofol increase in patients treated with angiotensin-converting enzyme inhibitors (ACEi). Given that both propofol and ACEi affect nitric oxide (NO) signaling, the present study tested the hypothesis that ACEi treatment induces pronounced hypotensive responses to propofol by increasing NO bioavailability. In this study we evaluated 65 patients, divided into three groups: hypertensive patients chronically treated with ACEi (HT-ACEi; n = 21), hypertensive patients treated with other antihypertensive drugs instead of ACEi, such as angiotensin II receptor blockers, β-blockers or diuretics (HT; n = 21) and healthy normotensive subjects (NT; n = 23). Venous blood samples were collected at baseline and after 10 min of anesthesia with propofol 2 mg/kg administrated intravenously by bolus injection. Hemodynamic parameters were recorded at each blood sample collection. Nitrite levels were determined by using an ozone-based chemiluminescence assay, while NOx (nitrites+nitrates) levels were measured by using the Griess reaction. Additionally, experimental approaches were used to validate our clinical findings. Higher decreases in blood pressure after propofol anesthesia were observed in HT-ACEi group as compared with those found in NT and HT groups. Consistently, rats treated with the ACEi enalapril showed more intense hypotensive responses to propofol. The hypotensive effects of propofol were associated with increased NO production in both clinical and experimental approaches. Enhanced increases in nitrite levels after propofol anesthesia were observed in HT-ACEi patients compared with NT and HT groups. Accordingly, rats treated with enalapril showed increased vascular NO formation after propofol anesthesia compared with rats receiving vehicle. Our data show that ACEi enhance the hypotensive responses to propofol anesthesia and increase nitrite concentrations. These findings suggest that increased NO bioavailability may account for the enhanced hypotensive effects of propofol in ACEi-treated patients.
  • References (39)
  • Citations (2)
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References39
Newest
Published on Jan 1, 2016in Gene2.64
Gustavo H. Oliveira-Paula9
Estimated H-index: 9
(USP: University of São Paulo),
Riccardo Lacchini16
Estimated H-index: 16
(USP: University of São Paulo),
Jose E. Tanus-Santos34
Estimated H-index: 34
(USP: University of São Paulo)
ABSTRACT Nitric oxide (NO) is an important vasodilator with a well-established role in cardiovascular homeostasis. While mediator is synthesized from L-arginine by neuronal, endothelial, and inducible nitric oxide synthases (NOS1, NOS3 and NOS2 respectively), NOS3 is the most important isoform for NO formation in the cardiovascular system. NOS3 is a dimeric enzyme whose expression and activity are regulated at transcriptional, posttranscriptional, and posttranslational levels. The NOS3 gene, whi...
Published on Sep 1, 2015in Journal of Cardiovascular Pharmacology2.37
Yan Wang1
Estimated H-index: 1
,
Huixuan Zhou1
Estimated H-index: 1
+ 3 AuthorsLi Wang5
Estimated H-index: 5
Abstract Protein kinase C (PKC) isoforms improve endothelial nitric oxide synthase activity and contractile Ca sensitivity in blood vessels. These actions may have opposite effects on propofol-induced vasodilation. This study examines the hypothesis that propofol induces relaxation by enhancing the PKC-mediated nitric oxide synthesis in endothelium and/or inhibiting the PKC-regulated Ca sensitivity in vascular smooth muscle (VSM). Propofol (1-100 μM) induced greater relaxation in endothelium-int...
Published on Jun 1, 2015in British Journal of Clinical Pharmacology3.87
Dimitrios Tsikas50
Estimated H-index: 50
(MHH: Hannover Medical School),
Jens Jordan60
Estimated H-index: 60
(MHH: Hannover Medical School),
Stefan Engeli39
Estimated H-index: 39
(MHH: Hannover Medical School)
Blood pressure (BP) reduction is a common pharmacodynamic feature of propofol, sevoflurane and other drugs used in general anaesthesia. The mechanisms by which propofol induces anaesthesia have been discussed 1,2. During total intravenous anaesthesia with propofol and sevoflurane anaesthesia, systolic and diastolic BP decreased by ∼30% 3–5. The underlying BP-lowering mechanisms of propofol and other anaesthetics are incompletely understood. Propofol is likely to induce hypotension by inhibiting ...
Published on Apr 1, 2015in PLOS ONE2.78
Sayantani Sinha2
Estimated H-index: 2
(KSU: Kent State University),
Pritam Sinharoy5
Estimated H-index: 5
(KSU: Kent State University)
+ 1 AuthorsDerek S. Damron8
Estimated H-index: 8
(KSU: Kent State University)
Background Transient receptor potential (TRP) ion channels of the A1 (TRPA1) and V1 (TRPV1) subtypes are key regulators of vasomotor tone. Propofol is an intravenous anesthetic known to cause vasorelaxation. Our objectives were to examine the extent to which TRPA1 and/or TRPV1 ion channels mediate propofol-induced depressor responses in vivo and to delineate the signaling pathway(s) involved. Methods Mice were subjected to surgery under 1.5–2.5% sevoflurane gas with supplemental oxygen. After a ...
Published on Jun 1, 2014in Basic & Clinical Pharmacology & Toxicology2.45
Vanessa Fontana14
Estimated H-index: 14
(State University of Campinas),
Ana Paula Faria10
Estimated H-index: 10
(State University of Campinas)
+ 4 AuthorsHeitor Moreno Junior31
Estimated H-index: 31
(State University of Campinas)
Activation of the renin-angiotensin-aldosterone system (RAAS) and abnormal adipokine levels are biological alterations that affect blood pressure regulation and interact to link hypertension, obesity and metabolic diseases. While imbalanced levels of hormones produced by adipocytes including hypo-adiponectinaemia and hyperleptinaemia were reported in hypertension, little is known about how antihypertensive therapy affects these alterations. This study aimed to evaluate the effects of enalapril o...
Published on Apr 1, 2013in Anesthesia & Analgesia3.49
Ferrante S. Gragasin9
Estimated H-index: 9
(U of A: University of Alberta),
Stephane L. Bourque12
Estimated H-index: 12
,
Sandra T. Davidge52
Estimated H-index: 52
BACKGROUND: Both propofol use and advanced age are predictors of intraoperative hypotension. We previously demonstrated that propofol enhances vasodilation in mesenteric arteries from aged rats, partly due to increased nitric oxide (NO) bioavailability. Patients chronically treated with angiotensin-converting enzyme (ACE) inhibitors may exhibit refractory hypotension under general anesthesia. We hypothesized that propofol enhances NO-mediated vasodilation in arteries from aged rats chronically t...
Published on Jan 1, 2013in Nitric Oxide3.37
Ingrid F. Metzger14
Estimated H-index: 14
(USP: University of São Paulo),
Marcelo R. Luizon14
Estimated H-index: 14
(USP: University of São Paulo)
+ 2 AuthorsJose E. Tanus-Santos34
Estimated H-index: 34
(USP: University of São Paulo)
Abstract Haplotypes formed by clinically relevant polymorphisms in the endothelial nitric oxide synthase ( eNOS ) gene have been associated with variations in endogenous nitric oxide (NO) formation in white and black subjects. We examined whether further genetic variation and haplotypes of the eNOS gene, represented by the rs3918188, rs743506 and rs7830 tagSNPs (polymorphisms that represent the information of neighboring SNPs in linkage disequilibrium) affect endogenous NO formation in 181 healt...
Published on Dec 1, 2012in Cardiovascular Drugs and Therapy4.18
Vanessa Fontana14
Estimated H-index: 14
(USP: University of São Paulo),
Pamela S. Silva8
Estimated H-index: 8
(State University of Campinas)
+ 4 AuthorsJose E. Tanus-Santos34
Estimated H-index: 34
(USP: University of São Paulo)
Purpose Angiotensin-converting enzyme inhibitors (ACEi) may downregulate matrix metalloproteinases (MMPs). We examined whether enalapril affects MMP-2, MMP-8, and MMP-9 levels and activity, and their endogenous inhibitors (tissue inhibitors of MMPs, TIMP-1 and TIMP-2) levels in hypertensive patients. Moreover, we assessed the effects of enalaprilat on MMP-9 and TIMP-1 secretion by human endothelial cells (HUVECs).
Published on Oct 1, 2011in BJA: British Journal of Anaesthesia6.20
Jiawei Chen10
Estimated H-index: 10
(Fudan University),
Wei Chen3
Estimated H-index: 3
(Fudan University)
+ 3 AuthorsZhiming Tan13
Estimated H-index: 13
(Fudan University)
Background Angiotensin II (Ang II) induces oxidative stress and apoptosis in vascular endothelial cells. We hypothesized that propofol may attenuate Ang II-induced apoptosis in human coronary artery endothelial cells (HCAECs) and aimed to identify the underlying mechanisms. Methods Endothelial cells were pre-treated with propofol and then stimulated with Ang II. Apoptosis was examined by TUNEL, DNA laddering, and caspase-3 activity assays. The effect of propofol on Ang II-modulated NADPH oxidase...
Published on Apr 1, 2011in European Journal of Clinical Pharmacology2.77
Pamela S. Silva8
Estimated H-index: 8
(State University of Campinas),
Vanessa Fontana14
Estimated H-index: 14
(USP: University of São Paulo)
+ 3 AuthorsJosé Eduardo Tanus-Santos27
Estimated H-index: 27
(USP: University of São Paulo)
Purpose The antihypertensive effects of angiotensin-converting enzyme inhibitors (ACEi) are explained, at least in part, by enhanced bradykinin-dependent nitric oxide (NO) formation and decreased angiotensin II-induced oxidative stress and vasoconstriction. We examined for the first time whether treatment with enalapril increases the plasma levels of markers of NO formation and decreases oxidative stress in mild to moderate hypertensive patients.
Cited By2
Newest
Published on Jan 25, 2019in Current Drug Targets2.64
Gustavo H. Oliveira-Paula9
Estimated H-index: 9
(USP: University of São Paulo),
Jose E. Tanus-Santos34
Estimated H-index: 34
(USP: University of São Paulo)
Published on May 1, 2018in Nitric Oxide3.37
Gustavo H. Oliveira-Paula9
Estimated H-index: 9
(USP: University of São Paulo),
Riccardo Lacchini16
Estimated H-index: 16
(USP: University of São Paulo)
+ 5 AuthorsJose E. Tanus-Santos34
Estimated H-index: 34
(USP: University of São Paulo)
Abstract Propofol anesthesia is usually accompanied by hypotension, which is at least in part related to enhanced endothelial nitric oxide synthase (NOS3)-derived NO bioavailability. We examined here whether NOS3 polymorphisms (rs2070744, 4b/4a VNTR, rs3918226 and rs1799983) and haplotypes affect the changes in blood pressure and NO bioavailability induced by propofol. Venous blood samples were collected from 168 patients at baseline and after 10 min of anesthesia with propofol 2 mg/kg administe...