Genetic determinants of vascular reactivity

Henrion, Didier; Bénessiano, Joëlle; Iglarz, Marc; Philip, Ivan; Lévy, Bernard

doi:10.1007/s11906-002-0052-z

Cited by 5 publications

(6 citation statements)

References 55 publications

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“…1) as follows: (1) dysregulation of the sympathetic nervous system causes obesity and dyslipidaemia [11]; (2) dysregulation of lipogenesis and lipoprotein metabolism causes ectopic fat deposition, dyslipidaemia, inflammation and insulin resistance [12][13][14][15]; (3) abnormalities in stress and natriuretic responses and vascular reactivity contribute to hypertension [16,17] Fig. 1 The first component of SEM comprises a factor analysis model, in which closely correlated measured variables (in rectangles) are loaded onto latent factors (in ovals) to give a more precise interpretation.…”

Section: Introductionmentioning

confidence: 99%

Phenotype–genotype interactions on renal function in type 2 diabetes: an analysis using structural equation modelling

Song

Lee

et al. 2009

Diabetologia

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Aims/hypothesis Cardiovascular and renal diseases share common risk factors. We used structural equation modelling (SEM) to evaluate the independent and combined effects of phenotypes and genotypes implicated in cardiovascular diseases on renal function in type 2 diabetes.Methods 1,188 type 2 diabetic patients were stratified into high-risk and low-risk groups according to bimodal distributions of the logarithmically transformed (log e ) urinary albumin:creatinine ratio and plasma creatinine levels. Models for these groups, comprising continuous and non-ranking categorical data, were developed separately to evaluate the inter-relationships among measured variables and latent factors using non-linear SEMs, Bayesian estimation and model selection as assessed by a goodness-of-fit statistic. Results Inter-correlated measured variables (obesity, glycaemia, lipid, blood pressure) and variants of the genes encoding endothelial nitric oxide synthase (NOS), β-adrenergic receptor (ADRB), components of the reninangiotensin system (RAS) and lipid metabolism were loaded onto their respective latent factors of phenotypes and genotypes. In addition to direct and indirect effects, latent factors of obesity, lipid and BP interacted with latent factors of ADRB and RAS genotypes to influence renal function. Together with variants of the genes encoding peroxisome proliferator-activated receptor γ, atrial natriuretic peptide, adducin, G protein β 3 subunit, epithelial sodium channel α subunit and matrix metallopeptidase 3, these parameters explained 39-80% of the variance in renal function in the high-risk and low-risk models. Conclusions/interpretation SEM is a useful tool for confirming and quantifying multiple interactions of biological pathways with genetic determinants. The combined and interactive effects of blood pressure, lipid and obesity on renal function may have therapeutic implications, especially in type 2 diabetic individuals with genetic risk factors.

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Section: Introductionmentioning

confidence: 99%

Phenotype–genotype interactions on renal function in type 2 diabetes: an analysis using structural equation modelling

Song

Lee

et al. 2009

Diabetologia

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“…Other possibilities include a direct pro-hypertrophic effect of tissue RAAS upregulation or to high myocardial oxygen demands in the high-risk group with a resulting failure to decrease stroke volume. High myocardial oxygen consumption has been previously reported in patients with high-risk RAAS genotypes, in particular the ACE DD genotype, especially during conditions with increased metabolic requirements 37, 32, 38, 39 .…”

Section: Discussionmentioning

confidence: 86%

Renin-Angiotensin-Aldosterone Genotype Influences Ventricular Remodeling in Infants With Single Ventricle

et al. 2011

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Background We investigated the effect of polymorphisms in the renin-angiotensin-aldosterone system (RAAS) genes on ventricular remodeling, growth, renal function and response to enalapril in infants with single ventricle. Methods and Results Single ventricle infants enrolled in a randomized trial of enalapril were genotyped for polymorphisms in 5 genes: angiotensinogen, angiotensin-converting enzyme, angiotensin II type 1 receptor, aldosterone synthase, and chymase. Alleles associated with RAAS upregulation were classified as risk alleles. Ventricular mass, volume, somatic growth, renal function using estimated glomerular filtration rate (eGFR), and response to enalapril were compared between patients with ≥2 homozygous risk genotypes (high-risk), and those with <2 homozygous risk genotypes (low-risk) at two time points - before the superior-cavopulmonary-connection (pre-SCPC) and at age 14 months. Of 230 trial subjects, 154 were genotyped: 38 were high-risk, 116 were low-risk. Ventricular mass and volume were elevated in both groups pre-SCPC. Ventricular mass and volume decreased and eGFR increased after SCPC in the low-risk (p<0.05) but not the high-risk group. These responses were independent of enalapril treatment. Weight and height z-scores were lower at baseline and height remained lower in the high-risk group at 14 months especially in those receiving enalapril (p<0.05). Conclusions RAAS-upregulation genotypes were associated with failure of reverse remodeling after SCPC surgery, less improvement in renal function, and impaired somatic growth, the latter especially in patients receiving enalapril. RAAS genotype may identify a high-risk subgroup of single ventricle patients who fail to fully benefit from volume unloading surgery. Follow-up is warranted to assess longterm impact. Clinical Trial Registration Clinical Trials.gov Identifier NCT00113087

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“…This raises the point of a potential genetic driver of cerebrovascular response to particular vasopressors. Genetic polymorphisms within adrenoreceptors have been increasingly linked to hypertension and cardiovascular disease [16]. For example, the alpha 2B adrenergic insertion/deletion polymorphism has demonstrated greater degrees of peripheral vasoconstriction when stimulated with an alpha 2 agonist, dexmedetomidine, compared to controls [17].…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, alterations in the beta 2 adrenoreceptor have been linked to refractory hypertension, related to impaired vasodilatory effects when stimulated. Endothelin-1, angiotensin II, and nitric oxide-cGMP pathway polymorphisms have also been linked to altered adrenergic vascular reactivity and are associated with hypertension [16]. All of the mentioned polymorphisms could contribute to undesired cerebrovascular reactivity to adrenergic stimulation with vasopressor agents.…”

Section: Discussionmentioning

confidence: 99%

Norepinephrine as a Potential Aggravator of Symptomatic Cerebral Vasospasm: Two Cases and Argument for Milrinone Therapy

Zeiler

Silvaggio

Kaufmann

et al. 2014

Case Reports in Critical Care

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Background. During hypertensive therapy for post-subarachnoid hemorrhage (SAH) symptomatic vasospasm, norepinephrine is commonly used to reach target blood pressures. Concerns over aggravation of vasospasm with norepinephrine exist. Objective. To describe norepinephrine temporally related deterioration in neurological examination of two post-SAH patients in vasospasm. Methods. We retrospectively reviewed two charts of patients with delayed cerebral ischemia (DCI) post-SAH who deteriorated with norepinephrine infusions. Results. We identified two patients with DCI post-SAH who deteriorated during hypertensive therapy with norepinephrine. The first, a 43-year-old male presented to hospital with DCI, failed MABP directed therapy with rapid deterioration in exam with high dose norepinephrine and MABP of 140–150 mm Hg. His exam improved on continuous milrinone and discontinuation of norepinephrine. The second, a 39-year-old female who developed DCI on postbleed day 8 responded to milrinone therapy upfront. During further deterioration and after angioplasty, norepinephrine was utilized to drive MABP to 130–140 mm Hg. Progressive deterioration in examination occurred after angioplasty as norepinephrine doses escalated. After discontinuation of norepinephrine and continuation of milrinone, function dramatically returned but not to baseline. Conclusions. The potential exists for worsening of DCI post-SAH with hypertensive therapy directed by norepinephrine. A potential role exists for vasodilation and inotropic directed therapy with milrinone in the setting of DCI post-SAH.

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Genetic determinants of vascular reactivity

Cited by 5 publications

References 55 publications

Phenotype–genotype interactions on renal function in type 2 diabetes: an analysis using structural equation modelling

Phenotype–genotype interactions on renal function in type 2 diabetes: an analysis using structural equation modelling

Renin-Angiotensin-Aldosterone Genotype Influences Ventricular Remodeling in Infants With Single Ventricle

Norepinephrine as a Potential Aggravator of Symptomatic Cerebral Vasospasm: Two Cases and Argument for Milrinone Therapy

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