Endothelial nitric oxide synthase polymorphisms affect the changes in blood pressure and nitric oxide bioavailability induced by propofol

Oliveira-Paula, Gustavo H.; Lacchini, Riccardo; Pinheiro, Lucas C.; Ferreira, Graziele C.; Luizon, Marcelo R.; Garcia, Waynice N.P.; Garcia, Luís Vicente; Tanus‐Santos, Jose E.

doi:10.1016/j.niox.2018.02.007

Cited by 15 publications

(9 citation statements)

References 49 publications

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“…Indeed, many of these effects are related to the vasodilation produced by nitric oxide (NO) as a result of endothelial NO synthase (NOS3) activation 104,105. NOS3 is the dominant NO synthase in the vasculature and polymorphisms in the gene encoding this enzyme have been associated with hypertension and other cardiovascular alterations 106–108. The pharmacogenomic relevance of NOS3 for ACE inhibitor and ARB responses has been shown in different studies.…”

Section: Angiotensin-converting Enzyme Inhibitors and Angiotensin II mentioning

confidence: 99%

<p>Pharmacogenomics And Hypertension: Current Insights</p>

Oliveira-Paula

Pereira

Tanus‐Santos

et al. 2019

PGPM

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Hypertension is a multifactorial disease that affects approximately one billion subjects worldwide and is a major risk factor associated with cardiovascular events, including coronary heart disease and cerebrovascular accidents. Therefore, adequate blood pressure control is important to prevent these events, reducing premature mortality and disability. However, only one third of patients have the effective control of blood pressure, despite several classes of antihypertensive drugs available. These disappointing outcomes may be at least in part explained by interpatient variability in drug response due to genetic polymorphisms. To address the effects of genetic polymorphisms on blood pressure responses to the antihypertensive drug classes, studies have applied candidate genes and genome wide approaches. More recently, a third approach that considers gene-gene interactions has also been applied in hypertension pharmacogenomics. In this article, we carried out a comprehensive review of recent findings on the pharmacogenomics of antihypertensive drugs, including diuretics, β-blockers, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, and calcium channel blockers. We also discuss the limitations and inconsistences that have been found in hypertension pharmacogenomics and the challenges to implement this valuable approach in clinical practice.

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Section: Angiotensin-converting Enzyme Inhibitors and Angiotensin II mentioning

confidence: 99%

<p>Pharmacogenomics And Hypertension: Current Insights</p>

Oliveira-Paula

Pereira

Tanus‐Santos

et al. 2019

PGPM

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“…Interestingly, studies have demonstrated that propofol promotes NOS3 activation and consequent NO formation in endothelial cells through the drug‐stimulated translocation of PKC 15,20 . In line with the critical role of NOS3 in propofol‐induced hypotension, we have recently found that NOS3 polymorphisms affect the blood pressure changes and NO bioavailability promoted by propofol 27 . However, if these polymorphisms interact with PRKCA polymorphisms to modify the hypotensive effects of propofol is unknown.…”

Section: Introductionmentioning

confidence: 77%

“…Genotypes for the NOS3 SNPs rs2070744, rs3918226 and rs1799983 were determined by Taqman Allele Discrimination Assays (Applied Biosystems, Foster City, CA, USA), and for the NOS3 4b/4a VNTR polymorphism were determined by PCR, as previously described. 27,33…”

Section: Genotypingmentioning

confidence: 99%

Gene–gene interactions in the protein kinase C/endothelial nitric oxide synthase axis impact the hypotensive effects of propofol

Oliveira-Paula

Pereira

Pinheiro

et al. 2021

Basic Clin Pharma Tox

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Anaesthesia with propofol is frequently associated with hypotension, which is at least partially attributable to increased nitric oxide (NO) formation derived from the activation of protein kinase C (PKC)/endothelial NO synthase (NOS3) axis. In this cross‐sectional study, we tested whether PRKCA (which encodes PKCα) polymorphisms, or haplotypes, and interactions among PRKCA and NOS3 polymorphisms affect the hypotensive responses to propofol. We collected venous blood samples from 164 patients before and 10 min after propofol administration. Genotypes were determined by PCR and haplotype frequencies were estimated. Nitrite and NOx (nitrites+nitrates) levels were measured by using an ozone‐based chemiluminescence assay and the Griess reaction, respectively. We used multifactor dimensionality reduction to test interactions among PRKCA and NOS3 polymorphisms. Propofol promoted enhanced blood pressure‐lowering effects and increased nitrite levels in subjects carrying GA + AA genotypes for the rs16960228 and TC + CC genotypes for the rs1010544 PRKCA polymorphisms, and the CCG haplotype. Moreover, genotypes for the rs1010544 PRKCA polymorphism were associated with higher or lower blood pressure decreases in response to propofol depending on the genotypes for the rs2070744 NOS3 polymorphism. Our findings suggest that PRKCA genotypes and haplotypes impact the hypotensive responses to propofol, possibly by modifying NO bioavailability, and that PRKCA‐NOS3 interactions modify the blood pressure‐lowering effects of propofol.

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“…Propofol is a commonly used anesthetic drug in clinical settings, which has good anesthetic induction and maintenance effects, and is often used in radical surgery of tumors and postoperative sedation 18 . In addition to anesthesia, propofol also affects immunity, inflammation, and ischemia reperfusion injury 4,19 . Propofol has been reported to induce antitumor immunity by promoting T-assisted cell activation and differentiation [20][21][22] and can inhibit the viability, migration, and invasion of bladder cancer T24 cells in vitro 23 .…”

Section: Discussionmentioning

confidence: 99%

Propofol Inhibits the Proliferation, Migration, and Stem-like Properties of Bladder Cancer Mainly by Suppressing the Hedgehog Pathway

Zhang

Guo

et al. 2021

Cell Transplant

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Bladder cancer is one of the most common malignancies. The existence of bladder cancer stem cells (BCSCs) has been suggested to underlie bladder tumor initiation and recurrence. Propofol is a commonly used intravenous anesthetic. Here, we find that propofol can dramatically block the activation of Hedgehog pathway in BCSCs. The propofol strongly repressed the growth of cancer cells. Attenuated proliferation and enhanced apoptosis of tumor cells were observed upon propofol stimulation. Furthermore, propofol reduced the self-renewal ability of BCSCs as well as the tumor formation. In conclusion, propofol is potentially used as a novel therapeutic agent for bladder cancer by targeting self-renewal through inhibiting Hedgehog pathway.

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Endothelial nitric oxide synthase polymorphisms affect the changes in blood pressure and nitric oxide bioavailability induced by propofol

Cited by 15 publications

References 49 publications

<p>Pharmacogenomics And Hypertension: Current Insights</p>

<p>Pharmacogenomics And Hypertension: Current Insights</p>

Gene–gene interactions in the protein kinase C/endothelial nitric oxide synthase axis impact the hypotensive effects of propofol

Propofol Inhibits the Proliferation, Migration, and Stem-like Properties of Bladder Cancer Mainly by Suppressing the Hedgehog Pathway

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