Decreasing Nurses' Anxiety About Pediatric End-of-Life Care With Simulation.

BACKGROUND: Caring for pediatric patients at the end of life (EOL) can lead to anxiety and burnout for critical care nurses. New graduate nurses (NGNs) often report receiving inadequate education related to EOL care and then enter the workforce with limited clinical experience in caring for patients at EOL. A quality improvement project at a pediatric academic hospital sought to determine whether a simulation-based educational program for NGNs working in critical care could reduce anxiety about EOL care. METHOD: Eight NGNs participated in a case study and simulation-based educational program that encompassed topics such as communication, symptom management, postmortem care, and support for the family at EOL. Anxiety was measured pre- and postprogram with the Spielberger State-Trait Anxiety Inventory (STAI©). RESULTS: Anxiety levels after participation in the EOL educational program decreased by 24.1% from preprogram levels. CONCLUSION: Providing NGNs in critical care with a case- and simulation-based EOL educational program can reduce anxiety levels and potentially decrease caregiver burnout. [J Contin Educ Nurs. 2023;54(12):574-580.].

Single nucleotide polymorphisms and sickle cell disease-related pain: a systematic review.

Background: Scientists have speculated genetic variants may contribute to an individual's unique pain experience. Although research exists regarding the relationship between single nucleotide polymorphisms and sickle cell disease-related pain, this literature has not been synthesized to help inform future precision health research for sickle cell disease-related pain. Our primary aim of this systematic review was to synthesize the current state of scientific literature regarding single nucleotide polymorphisms and their association with sickle cell disease-related pain. Methods: Using the Prisma guidelines, we conducted our search between December 2021-April 2022. We searched PubMed, Web of Science, CINAHL, and Embase databases (1998-2022) and selected all peer-reviewed articles that included reports of associations between single nucleotide polymorphisms and sickle cell disease-related pain outcomes. Results: Our search yielded 215 articles, 80 of which were duplicates, and after two reviewers (GG, JD) independently screened the 135 non-duplicate articles, we retained 22 articles that met the study criteria. The synthesis of internationally generated evidence revealed that this scientific area remains predominantly exploratory in nature, with only three studies reporting sufficient power for genetic association. Sampling varied across studies with a range of children to older adults with SCD. All of the included articles (n = 22) examined acute pain, while only nine of those studies also examined chronic pain. Conclusion: Currently, the evidence implicating genetic variation contributing to acute and chronic sickle cell disease-related pain is characterized by modestly powered candidate-gene studies using rigorous SCD-pain outcomes. Effect sizes and directions vary across studies and are valuable for informing the design of future studies. Further research is needed to replicate these associations and extend findings with hypothesis-driven research to inform precision health research.

Symptom Presentation among Women with Suspected Ischemia and No Obstructive Coronary Artery Disease (INOCA).

Identifying ischemic heart disease (IHD) in women based on symptoms is challenging. Women are more likely to endorse non-cardiac symptoms. More than 50% of women with suspected ischemia have no obstructive coronary disease (and thus, INOCA) and impaired outcomes during follow-up. We aimed to identify symptoms having predictive capacity for INOCA in women with clinical evidence of coronary ischemia. We included 916 women from the original WISE cohort (NCT00000554) who had coronary angiography performed for suspected ischemia and completed a 65-item WISE symptom questionnaire. Sixty-two percent (n = 567) had suspected INOCA. Logistic regression models using a best subsets approach were examined to identify the best predictive model for INOCA based on Score χ2 and AICc. A 10-variable, best-fit model accurately predicted INOCA (AUC 0.72, 95% CI 0.68, 0.75). The model indicated that age ≤ 55 years, left side chest pain, chest discomfort, neck pain, and palpitations had independent, positive relationship (OR > 1) to INOCA (p < 0.001 to 0.008). An inverse relationship (OR < 1) was observed for impending doom, and pain in the jaw, left or bilateral arm, and right hand, interpreted as INOCA associated with the absence of these symptoms (p ≤ 0.001 to 0.023). Our best-fit model accurately predicted INOCA based on age and symptom presentation ~72% of the time. While the heterogeneity of symptom presentation limits the utility of this unvalidated 10-variable model, it has promise for consideration of symptom inclusion in future INOCA prediction risk modeling for women with evidence of symptomatic ischemia.

Sex-dimorphic gene effects on survival outcomes in people with coronary artery disease.

Background: Ischemic coronary heart disease (IHD) is the leading cause of death worldwide. Genetic variation is presumed to be a major factor underlying sex differences for IHD events, including mortality. The purpose of this study was to identify sex-specific candidate genes associated with all-cause mortality among people diagnosed with coronary artery disease (CAD). Methods: We performed a sex-stratified, exploratory genome-wide association (GWAS) screen using existing data from CAD-diagnosed males (n = 510) and females (n = 174) who reported European ancestry from the Duke Catheterization Genetics biorepository. Extant genotype data for 785,945 autosomal SNPs generated with the Human Omni1-Quad BeadChip (Illumina, CA, USA) were analyzed using an additive inheritance model. We estimated instantaneous risk of all-cause mortality by genotype groups across the 11-year follow-up using Cox multivariate regression, covarying for age and genomic ancestry. Results: The top GWAS hits associated with all-cause mortality among people with CAD included 8 SNPs among males and 15 among females (p = 1 × 10-6 or 10-7), adjusted for covariates. Cross-sex comparisons revealed distinct candidate genes. Biologically relevant candidates included rs9932462 (EMP2/TEKT5) and rs2835913 (KCNJ6) among males and rs7217169 (RAP1GAP2), rs8021816 (PRKD1), rs8133010 (PDE9A), and rs12145981 (LPGAT1) among females. Conclusions: We report 20 sex-specific candidate genes having suggestive association with all-cause mortality among CAD-diagnosed subjects. Findings demonstrate proof of principle for identifying sex-associated genetic factors that may help explain differential mortality risk in people with CAD. Replication and meta-analyses in larger studies with more diverse samples will strengthen future work in this area.

Relationship Between Psychosocial Stress and Blood Pressure: The National Heart, Lung, and Blood Institute Family Heart Study.

Introduction: Various domains of psychosocial stress have been significantly related to blood pressure. However, ambiguity is present in how these relationships are defined in the literature. Objective: To add to the existing literature and examine the relationship between psychosocial stress (financial strain and job strain) and other cofactors on blood pressure. Methods: This secondary analysis is designed to analyze the relationship between levels of job and financial stress and blood pressure outcomes among participants in the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study 2004-2008. The descriptive, cross-sectional design uses data from a subset of study participants, 350 White and 195 Black (n = 545), 338 female (62%), and all aged 18-56 years. Psychosocial stress was measured using the Singh Stress Scale. Resting systolic (SBP) and diastolic (DBP) blood pressure values obtained on a stress reactivity protocol day in the primary study, as well as calculated mean arterial pressure (MAP) were used for this analysis. Multivariate linear regression analyses were used to explore the relationship between psychosocial stress and blood pressure. Results: In this young cohort, self-report of either financial strain or job strain was associated with lower blood pressure levels than those of participants who reported neither stressor. Differential sex and race effects appear to contribute to these results. Blood pressure levels were not significantly associated with self-report of both stressors. Conclusion: Understanding the effects of various forms of stress on blood pressure may inform more precise HTN risk-factor screening and interventions to improve BP management.

Corrigendum: Genome-Wide Variants Associated With Longitudinal Survival Outcomes Among Individuals With Coronary Artery Disease.

[This corrects the article DOI: 10.3389/fgene.2021.661497.].

Genome-Wide Variants Associated With Longitudinal Survival Outcomes Among Individuals With Coronary Artery Disease.

OBJECTIVE: Coronary artery disease (CAD) is an age-associated condition that greatly increases the risk of mortality. The purpose of this study was to identify gene variants associated with all-cause mortality among individuals with clinically phenotyped CAD using a genome-wide screening approach. APPROACH AND RESULTS: We performed discovery (n = 1,099), replication (n = 404), and meta-analyses (N = 1,503) for association of genomic variants with survival outcome using secondary data from White participants with CAD from two GWAS sub-studies of the Duke Catheterization Genetics Biorepository. We modeled time from catheterization to death or last follow-up (median 7.1 years, max 12 years) using Cox multivariable regression analysis. Target statistical screening thresholds were p × 10-8 for the discovery phase and Bonferroni-calculated p-values for the replication (p < 5.3 × 10-4) and meta-analysis (p < 1.6 × 10-3) phases. Genome-wide analysis of 785,945 autosomal SNPs revealed two SNPs (rs13007553 and rs587936) that had the same direction of effect across all three phases of the analysis, with suggestive p-value association in discovery and replication and significant meta-analysis association in models adjusted for clinical covariates. The rs13007553 SNP variant, LINC01250, which resides between MYTIL and EIPR1, conferred increased risk for all-cause mortality even after controlling for clinical covariates [HR 1.47, 95% CI 1.17-1.86, p(adj) = 1.07 × 10-3 (discovery), p(adj) = 0.03 (replication), p(adj) = 9.53 × 10-5 (meta-analysis)]. MYT1L is involved in neuronal differentiation. TSSC1 is involved in endosomal recycling and is implicated in breast cancer. The rs587936 variant annotated to DAB2IP was associated with increased survival time [HR 0.65, 95% CI 0.51-0.83, p(adj) = 4.79 × 10-4 (discovery), p(adj) = 0.02 (replication), p(adj) = 2.25 × 10-5 (meta-analysis)]. DAB2IP is a ras/GAP tumor suppressor gene which is highly expressed in vascular tissue. DAB2IP has multiple lines of evidence for protection against atherosclerosis. CONCLUSION: Replicated findings identified two candidate genes for further study regarding association with survival in high-risk CAD patients: novel loci LINC01250 (rs13007553) and biologically relevant candidate DAB2IP (rs587936). These candidates did not overlap with validated longevity candidate genes. Future research could further define the role of common variants in survival outcomes for people with CAD and, ultimately, improve longitudinal outcomes for these patients.

Protein Cytokines, Cytokine Gene Polymorphisms, and Potential Acute Coronary Syndrome Symptoms.

The purpose of this study was to determine whether relationships exist among protein cytokines, cytokine gene polymorphisms, and symptoms of potential acute coronary syndrome (ACS). Participants included 438 patients presenting to the emergency department (ED) whose symptoms triggered a cardiac evaluation (206 ruled in and 232 ruled out for ACS). Presence or absence of 13 symptoms was recorded upon arrival. Levels of tumor necrosis factor α (TNF-α), interleukin (IL)-6, and IL-18 were measured for all patients. A pilot analysis of 85 patients (ACS = 49; non-ACS = 36) genotyped eight single-nucleotide polymorphisms (SNPs; four TNF and four IL6 SNPs). Logistic regression models were tested to determine whether cytokines or SNPs predicted symptoms. Increased levels of TNF-α and IL-6 were associated with a decreased likelihood of chest discomfort for all patients. Increased levels of IL-6 were associated with a lower likelihood of chest discomfort and chest pressure for ACS patients, and an increased likelihood of shoulder and upper back pain for non-ACS patients. Elevated IL-18 was associated with an increased likelihood of sweating in patients with ACS. Of the four TNF SNPs, three were associated with shortness of breath, lightheadedness, unusual fatigue, and arm pain. In all, protein cytokines and TNF polymorphisms were associated with 11 of 13 symptoms assessed. Future studies are needed to determine the predictive ability of cytokines and related SNPs for a diagnosis of ACS or to determine whether biomarkers can identify patients with specific symptom clusters.

Polygenic signal for symptom dimensions and cognitive performance in patients with chronic schizophrenia.

Genetic etiology of psychopathology symptoms and cognitive performance in schizophrenia is supported by candidate gene and polygenic risk score (PRS) association studies. Such associations are reported to be dependent on several factors - sample characteristics, illness phase, illness severity etc. We aimed to examine if schizophrenia PRS predicted psychopathology symptoms and cognitive performance in patients with chronic schizophrenia. We also examined if schizophrenia associated autosomal loci were associated with specific symptoms or cognitive domains. Case-only analysis using data from the Clinical Antipsychotics Trials of Intervention Effectiveness-Schizophrenia trials (n = 730). PRS was constructed using Psychiatric Genomics Consortium (PGC) leave one out genome wide association analysis as the discovery data set. For candidate region analysis, we selected 105-schizophrenia associated autosomal loci from the PGC study. We found a significant effect of PRS on positive symptoms at p-threshold (PT ) of 0.5 (R2 = 0.007, p = 0.029, empirical p = 0.029) and negative symptoms at PT of 1e-07 (R2 = 0.005, p = 0.047, empirical p = 0.048). For models that additionally controlled for neurocognition, best fit PRS predicted positive (p-threshold 0.01, R2 = 0.007, p = 0.013, empirical p = 0.167) and negative symptoms (p-threshold 0.1, R2 = 0.012, p = 0.004, empirical p = 0.329). No associations were seen for overall neurocognitive and social cognitive performance tests. Post-hoc analyses revealed that PRS predicted working memory and vigilance performance but did not survive correction. No candidate regions that survived multiple testing corrections were associated with either symptoms or cognitive performance. Our findings point to potentially distinct pathogenic mechanisms for schizophrenia symptoms.

Unraveling interrelationships among psychopathology symptoms, cognitive domains and insight dimensions in chronic schizophrenia.

INTRODUCTION: Insight in schizophrenia is long known to have a complex relationship with psychopathology symptoms and cognition. However, very few studies have examined models that explain these interrelationships. METHODS: In a large sample derived from the NIMH Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial (N=1391), we interrogated these interrelationships for potential causal pathways using structural equation modeling. Using the NIMH consensus model, latent variables were constructed for psychopathology symptom dimensions, including positive, negative, disorganized, excited and depressed from the Positive and Negative Syndrome Scale (PANSS) items. Neurocognitive variables were created from five predefined domains of working memory, verbal memory, reasoning, vigilance and processing speed. Illness insight and treatment insight were tested using latent variables constructed from the Illness and Treatment Attitude Questionnaire (ITAQ). RESULTS: Disorganized symptoms had the strongest effect on insight. Illness insight mediated the relationship of positive, depressed, and disorganized symptoms with treatment insight. Neurocognition mediated the relationship between disorganized and treatment insight and depressed symptoms and treatment insight. There was no effect of negative symptoms on either illness insight or treatment insight. Taken together, our results indicate overlapping and unique relational paths for illness and treatment insight dimensions, which could suggest differences in causal mechanisms and potential interventions to improve insight.

Genetic correlates of insight in schizophrenia.

Insight in schizophrenia is clinically important as it is associated with several adverse outcomes. Genetic contributions to insight are unknown. We examined genetic contributions to insight by investigating if polygenic risk scores (PRS) and candidate regions were associated with insight. METHOD: Schizophrenia case-only analysis of the Clinical Antipsychotics Trials of Intervention Effectiveness trial. Schizophrenia PRS was constructed using Psychiatric Genomics Consortium (PGC) leave-one out GWAS as discovery data set. For candidate regions, we selected 105 schizophrenia-associated autosomal loci and 11 schizophrenia-related oligodendrocyte genes. We used regressions to examine PRS associations and set-based testing for candidate analysis. RESULTS: We examined data from 730 subjects. Best-fit PRS at p-threshold of 1e-07 was associated with total insight (R2=0.005, P=0.05, empirical P=0.054) and treatment insight (R2=0.005, P=0.048, empirical P=0.048). For models that controlled for neurocognition, PRS significantly predicted treatment insight but at higher p-thresholds (0.1 to 0.5) but did not survive correction. Patients with highest polygenic burden had 5.9 times increased risk for poor insight compared to patients with lowest burden. PRS explained 3.2% (P=0.002, empirical P=0.011) of variance in poor insight. Set-based analyses identified two variants associated with poor insight- rs320703, an intergenic variant (within-set P=6e-04, FDR P=0.046) and rs1479165 in SOX2-OT (within-set P=9e-04, FDR P=0.046). CONCLUSION: To the best of our knowledge, this is the first study examining genetic basis of insight. We provide evidence for genetic contributions to impaired insight. Relevance of findings and necessity for replication are discussed.

Pharmacogenetics of Ketamine-Induced Emergence Phenomena: A Pilot Study.

BACKGROUND: Up to 55% of patients who are administered ketamine experience an emergence phenomena (EP) that closely mimics schizophrenia and increases their risk of injury; however, to date, no studies have investigated genetic association of ketamine-induced EP in healthy patients. OBJECTIVES: The aim of the study was to investigate the feasibility and sample sizes required to explore the relationship between CYP2B6*6 and GRIN2B single-nucleotide polymorphisms and ketamine-induced EP. METHODS: This cross-sectional, pharmacogenetic candidate, gene pilot study recruited 75 patients having minor elective outpatient surgeries. EP was measured with the Clinician Administered Dissociative State Scale. Genetic association of CYP2B6*6 and GRIN2B (rs1019385 and rs1806191) single-nucleotide polymorphisms and ketamine-induced EP occurrence and severity were tested using logistic and linear regression. RESULTS: Forty-seven patients (63%) received ketamine and were genotyped, and 40% of them experienced EP. Occurrence and severity of EP were not associated with CYP2B6*6 or GRIN2B (p > .10). Exploratory analysis of nongenotype models containing age, ketamine dose, duration of anesthesia, and time from ketamine administration to assessment for EP significantly predicted EP occurrence (p = .001) and severity (p = .007). This pilot study demonstrates feasibility for implementing a pharmacogenetic study in a clinical setting, and we estimate that between 380 and 570 cases will be needed to adequately power future genetic association studies. DISCUSSION: Younger age, higher dose, and longer duration of anesthesia significantly predicted EP occurrence and severity among our pilot sample. Although the small sample size limited our ability to demonstrate significant genotype differences, we generated effect sizes, sample size estimates, and nongenetic covariates information in order to support future pharmacogenetic study design for evaluating this adverse event.

Pharmacogenetics of Anesthesia: An Integrative Review.

BACKGROUND: Monitoring a patient's response to drug therapy and early identification of an adverse reaction are important responsibilities of nurses. Despite the relative safety of anesthesia practice, 1 in 20 perioperative medication administrations includes a medication error and/or adverse drug reaction. Although several factors contribute to an individual's response to medications, genetic predisposition accounts for over 50% of that response. OBJECTIVE: The purpose of this review is to explore the evidence of genetic variability associated with response to volatile and intravenous anesthetics. METHODS: A comprehensive search of published literature in PubMed, CINAHL, and Cochrane databases from 1960 to May 30, 2015, was performed. Iterative reading of the primary articles was performed to ensure congruence between the extracted data and the primary article and reduce the data to draw conclusions. RESULTS: The analysis revealed that most anesthetics are metabolized by enzymes in the CYP2 and UGT1 family. CYP2B6 catalyzes propofol and ketamine metabolism. CYP2B6*6 allele is associated with decreased propofol and ketamine metabolism and increased adverse effects. Genetic variants in the UGT1A9 enzyme are associated with the need for higher induction dose and increased clearance of propofol. DISCUSSION: Despite the significant gaps in the literature, current evidence suggests that close monitoring is required when administering anesthetics to individuals with the CYP2B6*6 allele. Future research to address identified gaps in this review may have the potential to identify underlying genetic contribution to anesthetic response and prevent significant adverse events during anesthesia delivery and perioperative nursing care.

Case-Only Survival Analysis Reveals Unique Effects of Genotype, Sex, and Coronary Disease Severity on Survivorship.

Survival bias may unduly impact genetic association with complex diseases; gene-specific survival effects may further complicate such investigations. Coronary artery disease (CAD) is a complex phenotype for which little is understood about gene-specific survival effects; yet, such information can offer insight into refining genetic associations, improving replications, and can provide candidate genes for both mortality risk and improved survivorship in CAD. Building on our previous work, the purpose of this current study was to: evaluate LSAMP SNP-specific hazards for all-cause mortality post-catheterization in a larger cohort of our CAD cases; and, perform additional replication in an independent dataset. We examined two LSAMP SNPs-rs1462845 and rs6788787-using CAD case-only Cox proportional hazards regression for additive genetic effects, censored on time-to-all-cause mortality or last follow-up among Caucasian subjects from the Catheterization Genetics Study (CATHGEN; n = 2,224) and the Intermountain Heart Collaborative Study (IMHC; n = 3,008). Only after controlling for age, sex, body mass index, histories of smoking, type 2 diabetes, hyperlipidemia and hypertension (HR = 1.11, 95%CI = 1.01-1.22, p = 0.032), rs1462845 conferred significantly increased hazards of all-cause mortality among CAD cases. Even after controlling for multiple covariates, but in only the primary cohort, rs6788787 conferred significantly improved survival (HR = 0.80, 95% CI = 0.69-0.92, p = 0.002). Post-hoc analyses further stratifying by sex and disease severity revealed replicated effects for rs1462845: even after adjusting for aforementioned covariates and coronary interventional procedures, males with severe burden of CAD had significantly amplified hazards of death with the minor variant of rs1462845 in both cohorts (HR = 1.29, 95% CI = 1.08-1.55, p = 0.00456; replication HR = 1.25, 95% CI = 1.05-1.49, p = 0.013). Kaplan-Meier curves revealed unique cohort-specific genotype effects on survival. Additional analyses demonstrated that the homozygous risk genotype ('A/A') fully explained the increased hazard in both cohorts. None of the post-hoc analyses in control subjects were significant for any model. This suggests that genetic effects of rs1462845 on survival are unique to CAD presence. This represents formal, replicated evidence of genetic contribution of rs1462845 to increased risk for all-cause mortality; the contribution is unique to CAD case status and specific to males with severe burden of CAD.

Nursing implications of personalized and precision medicine.

OBJECTIVES: Identify and discuss the nursing implications of personalized and precision oncology care. DATA SOURCES: PubMed, CINAHL. CONCLUSION: The implications in personalized and precision cancer nursing care include interpretation and clinical use of novel and personalized information including genetic testing; patient advocacy and support throughout testing, anticipation of results and treatment; ongoing chronic monitoring; and support for patient decision-making. Attention must also be given to the family and ethical implications of a personalized approach to care. IMPLICATIONS FOR NURSING PRACTICE: Nurses face increasing challenges and opportunities in communication, support, and advocacy for patients given the availability of advanced testing, care and treatment in personalized and precision medicine. Nursing education and continuing education, clinical decision support, and health systems changes will be necessary to provide personalized multidisciplinary care to patients, in which nurses play a key role.

The genetic basis for survivorship in coronary artery disease.

Survivorship is a trait characterized by endurance and virility in the face of hardship. It is largely considered a psychosocial attribute developed during fatal conditions, rather than a biological trait for robustness in the context of complex, age-dependent diseases like coronary artery disease (CAD). The purpose of this paper is to present the novel phenotype, survivorship in CAD as an observed survival advantage concurrent with clinically significant CAD. We present a model for characterizing survivorship in CAD and its relationships with overlapping time- and clinically-related phenotypes. We offer an optimal measurement interval for investigating survivorship in CAD. We hypothesize genetic contributions to this construct and review the literature for evidence of genetic contribution to overlapping phenotypes in support of our hypothesis. We also present preliminary evidence of genetic effects on survival in people with clinically significant CAD from a primary case-control study of symptomatic coronary disease. Identifying gene variants that confer improved survival in the context of clinically appreciable CAD may improve our understanding of cardioprotective mechanisms acting at the gene level and potentially impact patients clinically in the future. Further, characterizing other survival-variant genetic effects may improve signal-to-noise ratio in detecting gene associations for CAD.

Altered beta-2 adrenergic receptor gene expression in human clinical hypertension.

OBJECTIVES: The beta-2 adrenergic receptor is involved in mediating vasodilatation via neurohumoral and sympathetic nervous system pathways. Alterations in beta-2 adrenergic receptor gene expression (mRNA transcription) may contribute to the hypertensive phenotype. Human gene expression in clinical phenotypes remains largely unexplored due to ethical constraints involved in obtaining human tissue. We devised a method to obtain normally discarded internal mammary artery tissue from coronary artery bypass graft patients. We then investigated differences in hypertensive and normotensive participants' beta-2 adrenergic receptor gene expression in this tissue. METHODS: We collected arterial tissue samples from 46 coronary artery bypass patients in a surgical setting. Using 41 of the samples, we performed TaqMan real-time polymerase chain reaction (RT-PCR) and used the delta delta cycle threshold (DeltaDeltaCt) relative quantitation method for determination of fold-differences in gene expression between normotensive and hypertensive participants. The beta-2 adrenergic receptor target was normalized to glyceraldehyde-phosphate dehydrogenase. RESULTS: Participants with hypertension had significantly less-expressed beta-2 adrenoceptor gene (2.76-fold, p<.05) compared to normotensive participants. After Bonferroni correction, gene expression did not differ by race, gender, type/dose of beta-blocker prescribed, positive family history of hypertension, or diagnosis of diabetes mellitus type 2. CONCLUSIONS: These data support the possibility of a molecular basis for impaired adrenoceptor-mediated vascular tone in hypertension. Modification and extension of this research is required.