Migrating Populations and Health: Risk Factors for Cardiovascular Disease and Metabolic Syndrome.

PURPOSE OF REVIEW: To summarize results of recent studies of migrants in Europe and North America and ongoing efforts to adapt strategies to provide them with inclusive sensitive health care. RECENT FINDINGS: Major predisposing factors for developing hypertension, obesity, diabetes, and the metabolic syndrome in migrating populations and refugees were identified. Susceptibility to the metabolic syndrome is predominantly due to environmental factors and psychological stress. Acculturation also contributes to the emergence of cardiovascular (CV) risk factors in first-generation adult immigrants. Increased risk for later development of hypertension and dyslipidemia has also been detected in adolescent immigrants. Targets for public health efforts were based on data that show important differences in CV risk factors and prevalence of the metabolic syndrome among ethnic immigrant groups. Studies in young adults focused on lifestyle and dietary behaviors and perceptions about weight and body image, while the focus for older adults was end-of-life issues. Two important themes have emerged: barriers to health care, with a focus on cultural and language barriers, and violence and its impact on immigrants' mental health.

Immigration and Acculturation: Impact on Health and Well-Being of Immigrants.

Among migrants who arrived in the USA and Europe, communicable diseases such as dermatologic, gastrointestinal, and respiratory infections are frequent; non-communicable diseases including chronic diseases such as hypertension and diabetes, and vaccine-preventable diseases are also prevalent. Refugees are often not up to date on routine immunizations and screenings for chronic diseases and cancer. In addition, many immigrants have trauma-related mental health problems, which are often not addressed by the healthcare systems where they reside. Determining the healthcare needs of specific immigration groups should lead to the establishment of evidence-based guidelines for providing screening and healthcare services to immigrant populations, for the benefit of the individuals concerned, as well as the host countries.

Animal models in obesity and hypertension.

Although obesity is a well-known risk factor for hypertension, the mechanisms by which hypertension develops in obese patients are not entirely clear. Animal models of obesity and their different susceptibilities to develop hypertension have revealed some of the mechanisms linking obesity and hypertension. Adipose tissue is an endocrine organ secreting hormones that impact blood pressure, such as elements of the renin-angiotensin system whose role in hypertension have been established. In addition, the appetite-suppressing adipokine leptin activates the sympathetic nervous system via the melanocortin system, and this activation, especially in the kidney, increases blood pressure. Leptin secretion from adipocytes is increased in most models of obesity due to leptin resistance, although the resistance is often selective to the anorexigenic effect, while the susceptibility to the hypertensive effect remains intact. Understanding the pathways by which obesity contributes to increased blood pressure will hopefully pave the way to and better define the appropriate treatment for obesity-induced hypertension.

Renal and systemic effects of endothelin-1 in diabetic-hypertensive rats.

The Cohen-Rosenthal Diabetic Hypertensive rat (CRDH) is a unique animal model in which genetic hypertension and diabetes developed after crossbreeding of Cohen diabetic rats sensitive substrain (CDR) and spontaneously hypertensive rats (SHR). The present study examined: 1) The acute effects of ET-1 on the systemic and renal hemodynamics in CRDH rats, CDR, and SHR; 2) The expression of ET-1 and its receptors in the renal tissue of CRDH rats. Intravenous injection of ET-1 (1.0 nmol/kg) into anesthetized SHR rats resulted in a significant immediate depressor response (mean arterial pressure (MAP) decreased from 165 ± 3 to 124 ± 12 mmHg, p < 0.0001) followed by a minor hypertensive phase (MAP increased to 170 ± 2 mmHg). Simultaneously, the administration of ET-1 caused a significant decrease in renal blood flow (RBF) from 5.8 ± 0.9 ml/min to 3.2 ± 0.5 ml/min (p = 0.026). These responses were blunted in CRDH rats and CDR. Analysis of intra-renal blood flow by laser-Doppler in CRDH rats revealed that ET-1 injection caused a decrease in cortical blood flow (Δ = -12 ± 2.9%). However, in contrast to its well-known renal medullary vasodilatory effect, ET-1 produced a significant decline in the medulla blood flow (Δ = -17.5 ± 3.4%) (p = 0.0125). These findings suggest that CDR and CRDH rats have reduced sensitivity to vascular and renal action of ET-1. Furthermore, in the CRDH rats, the expected ET-1-induced medullary vasodilatation was abolished and even reversed into prolonged vasoconstriction.

Renin-Angiotensin Inhibition in Combating Malignancy: A Review.

Our previous review of the literature assessed the existing knowledge (until 2000) about the possible link between angiotensin-converting enzyme inhibitors (ACEIs) and factors influencing the development of malignancies. We reviewed the literature for reports of statistical associations (or lack thereof) between ACEi treatment and incidence of specific cancers (e.g. breast, gastrointestinal, and skin). We concluded then that results from the epidemiological studies are conflicting, even taking the different methodology and endpoints into consideration, and thus inconclusive. Further investigation is needed beyond the observation period of most of these studies, and additional experimental studies are needed also to study the mechanisms by which agents blocking the renin-angiotensin system may obtain their inhibitory effect on tumor growth and metastasis. The present review elaborates further with more recent evidence from numerous human clinical studies from the past two decades (including large epidemiological studies, and long-term prospective and retrospective studies) on a protective association between ACEi treatment and the prognosis of patients with specific cancer types, malignancy characteristics or stage. Moreover, treatment with ACEI/angiotensin receptor blockers represents an adjuvant therapy with synergistic effects to chemotherapy and may improve patient outcomes (i.e. progression-free survival, and prolonged overall survival) in different types of cancers.

Managing hypertension in the elderly in light of the changes during aging.

The natural rise in systolic blood pressure with age is often complicated by other co-morbidities. Pharmacokinetics and pharmacodynamics of antihypertensive drugs are altered during aging, resulting in decrease in absorption and function of the kidney and liver, as well as interactions and adverse reactions of antihypertensives with the often large number of medications taken by the elderly. The problem of compliance in the elderly that may be disrupted by depression, loss of memory, vascular dementia and other conditions that compromise cognition is also of concern. Despite the many issues facing healthcare providers in managing hypertension in the elderly, the benefits are extensively documented and warrant overcoming therapeutic inertia, especially in view of current access to well documented therapeutic options.

Can a polypill one single tablet combat different cardiovascular risk factors?

Polypharmacy is defined as the use of two or more drugs simultaneously. Cardiovascular drugs and antihypertensives are commonly prescribed for treatment of cardiovascular disease (CVD), especially in elderly patients. Recent studies in patients with a history of CVD demonstrated that the fixed-dose combination of cardiovascular drugs in a polypill retain their individual efficacy, safety, and tolerability, thus have the potential to improve medication adherence and multiple risk factor control, thereby improving patient outcomes in secondary cardiovascular prevention. Since the initial conception of the fixed-dose polypill, just over a decade ago, only six large randomized trials assessing the efficacy and safety of this innovative concept have been completed (one is still ongoing). The results demonstrate that the polypill therapy significantly improved adherence, lowered systolic blood pressure, and low-density lipoprotein cholesterol, compared with usual care, in patients at high risk for CVD, especially among those who were undertreated at baseline. Correspondingly, further studies showed that the strengths of the polypill include better adherence, equivalent or better risk factor control, and improved quality of life among polypill users, as compared with usual care. However, the long-term outcome of the polypill on CVD events and mortality are unavailable and are currently being studied in clinical trials.

Beneficial Effect of the SGLT2 Inhibitor Empagliflozin on Glucose Homeostasis and Cardiovascular Parameters in the Cohen Rosenthal Diabetic Hypertensive (CRDH) Rat.

The effectiveness of empagliflozin (EMPA), a sodium glucose cotransporter type 2 inhibitor, on the kidney, pancreas, and heart was investigated in the Cohen Rosenthal diabetic hypertensive rat model (CRDH rat). Six-week-old CRDH male rats were fed a sugar diet (SD) and treated with the compound EMPA (group Drug/SD) or respective comparator with vehicle (group Veh/SD). A control group was fed a regular diet without treatment (group Veh/P). Preventive treatment with EMPA was measured during 4 months of follow-up. The treatment effect was evaluated according to results observed after 4 months in group Drug/SD when compared to those in group Veh/SD. Significant effect resulted in the following parameters: enhancement of urinary glucose excretion in association with diuresis; amelioration of postprandial hyperglycemia and fasting blood glucose levels; and decrease in calculated Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) as well as lower systolic and diastolic blood pressures. At the end of treatment, EMPA preserved nephrin integrity in the kidney, reduced proteinuria, and prevented diabetes-induced damage to glomerular diaphragm structure. In the pancreas, EMPA demonstrated an impressive decrease in fatty infiltration and atrophy. Blood pressure was significantly reduced in the EMPA-treated group (15 ± 5.1 mm Hg, P < .05) in contrast to the vehicle and control groups. Finally, compared to controls, EMPA significantly reduced left ventricle (LV) mass and LV systolic dilatation, according to 2-dimensional echocardiography. The importance of the study lies in demonstrating the efficacy of an antidiabetic drug with beneficial effects on blood pressure, weight, kidney, and pancreas and a positive effect on the heart.

Therapeutic actions of allylmercaptocaptopril and captopril in a rat model of metabolic syndrome.

BACKGROUND: Hypertension often coexists with hyperlipidemia, insulin resistance, and glucose intolerance in metabolic syndrome. Allylmercaptocaptopril is a conjugate of the angiotensin-converting enzyme inhibitor captopril with allicin, an active principle in garlic with multiple beneficial actions on metabolic-syndrome abnormalities. We sought to test the hypothesis that the conjugation of allicin to captopril may confer additional therapeutic actions in metabolic disease. METHODS: We compared allylmercaptocaptopril (53.5 mg/kg/day orally for 60 days) to an equimolar dose of captopril (40 mg/kg/day) in the spontaneously hypertensive, obese rat (SHROB) model. RESULTS: Allylmercaptocaptopril prevented progressive weight gain, without a detectable effect on food intake. Both captopril and allylmercaptocaptopril lowered blood pressure, but allylmercaptocaptopril was more effective. Allylmercaptocaptopril, but not captopril, improved cardiac hypertrophy, as indicated by heart weight and ventricular-wall thickness. Allylmercaptocaptopril improved, whereas captopril impaired, oral glucose tolerance after a fast. Triglycerides were decreased by both captopril and allylmercaptocaptopril. Total cholesterol and non-HDL cholesterol were reduced by captopril but not by allylmercaptocaptopril. The SHROB rats developed severe glomerulosclerosis and renal failure. Allylmercaptocaptopril showed significant nephro-protection, as indicated by reductions in urinary protein loss, urinary protein-to-creatinine ratio, and plasma creatinine. Captopril showed the same trends and also prevented the decline of creatinine clearance. Finally, both allylmercaptocaptopril and captopril reduced the basal level of lipolysis in isolated abdominal adipocytes, and restored the response to catecholamine stimulation. CONCLUSIONS: Both captopril and allylmercaptocaptopril are effective in attenuating multiple abnormalities of metabolic syndrome. Allylmercaptocaptopril may have additional effectiveness on improving glucose tolerance, further lowering blood pressure, reducing cardiac hypertrophy, preventing weight gain, and protecting against renal disease.

Effect of lercanidipine on kidney microanatomy in Cohen-Rosenthal diabetic hypertensive rats.

The study was undertaken to determine the effect of treatment with the dihydropyridine-type calcium antagonist lercanidipine on the renal vasculature in Cohen-Rosenthal diabetic hypertensive rats, a genetic model of hypertension associated with type 2 diabetes mellitus. Eight animals were given a daily oral dose of 3 mg/kg lercanidipine in drinking water for 8 weeks, and 6 control animals received no treatment. The effects on blood pressure, glucose level, and kidney microanatomy were evaluated. Lercanidipine reduced systolic blood pressure and glucose level. In the control group small arteries and glomerular arterioles exhibited wall thickening and luminal narrowing. Lercanidipine administration prevented the changes in small-sized arteries and glomerular arterioles. The glomerular changes observed in the untreated Cohen-Rosenthal diabetic hypertensive rats were not seen in the lercanidipine-treated animals. Lercanidipine also had beneficial effects on the renal vasculature, suggesting that the compound may be considered for treating hypertension associated with diabetes.

[Ambulatory blood pressure monitoring in diabetic hypertensive patients].

This study aimed to evaluate the frequency of attenuated decline in nocturnal blood pressure (BP) in diabetic hypertensive patients, and characterize those who don't decrease BP during nighttime. A total of 61 hypertensive patients (26 males and 35 females, mean age 65.8+/-10) were included in the study. Patients were defined as hypertensive if their daytime pressure exceeded 140/90 (the definition relevant at the time of our study) or if they were on antihypertensive treatment. All patients underwent 24 hour Ambulatory BP Monitoring (ABPM) using Suntech Accutracker Dx. Subjects with nocturnal fall in SBP, DBP or MAP of less than 10% of daytime values were classified as non-dippers. Echocardiography and renal function were also evaluated. Two thirds of the subjects were non-dippers. The percentage of dippers among women was higher than that observed in men: SBP 34% versus 19% and DBP 48% versus 38% (the difference is statistically significant with p< 0.01). Non-significant correlation was observed between absence of nocturnal decline, age and gender. The 24 hour ABPM measurements should be recommended in all diabetic hypertensive patients in whom aggressive treatment covering nighttime should be offered.

Telmisartan-mediated metabolic profile conferred brain protection in diabetic hypertensive rats as evidenced by magnetic resonance imaging, behavioral studies and histology.

Type 2 diabetes and hypertension are associated with cognitive dysfunction that includes pathological changes in brain tissue. It was speculated that the beneficial hypotensive effect of telmisartan, an angiotensin receptor 1 blocker, and its unique hypoglycemic effect due to its PPARγ-activation, could ameliorate the ​ pathological changes in the brain​ that accompany​ these diseases. We examined the effect of telmisartan on brain changes in magnetic resonance imaging (MRI) T2-weighted scans, and behavioral and histological findings in the Cohen-Rosenthal Diabetic Hypertensive (CRDH) rat. Baseline and post-treatment values with telmisartan/vehicle (3 months) of blood pressure, blood glucose levels, behavioral tests, brain MRI scanning and immunohistological staining were obtained. Telmisartan significantly lowered blood pressure and blood glucose levels; induced consistent T2 reduction in specific gray and white regions including hippocampus, corpus callosum, amygdala and cortical regions; and significantly improved performance on behavioral tasks. Immunohistological analysis of the brain revealed significant amelioration of diabetes/hypertension-induced changes in white matter regions and microglia, evidenced by preserved myelin (LBF marker), and improved microglial neuronal markers GFAP, GAP43 and Iba1 expression. In conclusion, the behavioral performance, longitudinal MRI study and histology staining revealed the protective effects of telmisartan on brain microstructure and cognitive function.

The effects of S-allylmercaptocaptopril, the synthetic product of allicin and captopril, on cardiovascular risk factors associated with the metabolic syndrome.

Pure allicin, prepared biosynthetically by reacting synthetic alliin with an immobilized alliinase enzyme, is known to possess cardioprotective effects. However, in its pure form, allicin is pharmacologically unstable. S-allylmercaptocaptopril (CPSSA) is a new stable synthetic compound produced by chemical reaction between allicin and the angiotensin converting enzyme inhibitor captopril. Using the fructose-induced metabolic syndrome rat model we studied the effects of short-term treatment with two doses of CPSSA on cardiovascular risk factors associated with the metabolic syndrome, in comparison to the effects of allicin and captopril separately. Allicin (8 mg/(kg day)) significantly reduced insulin, triglycerides, and homocysteine concentrations, and had a slight effect on SBP. Captopril (50mg/(kg day)) only improved blood pressure and homocysteine. Treatment with low dose of CPSSA (5mg/(kg day)) lowered SBP but did not improve any other measured parameter, while treatment with a higher dose (50mg/(kg day)) significantly decreased blood pressure, triglycerides, and homocysteine concentrations. We conclude that the combined molecule CPSSA integrates the anti-hypertensive, lipid-lowering, and homocysteine-reducing effects of both allicin and captopril, making it a potential cardiovascular protective agent.

Risk reduction therapy for syndrome X: comparison of several treatments.

BACKGROUND: Syndrome X, also termed the metabolic syndrome, is a cluster of physiologic and metabolic abnormalities including abdominal obesity, hyperinsulinemia, dyslipidemia and hypertension. Severe cardiovascular morbidity is associated with this pre-diabetic syndrome. We recently suggested that hyperhomocysteinemia is affiliated with this syndrome and thereby contributes to the vascular risk accompanying this condition. The present study compared the effects of antihypertensive, lipid-lowering, and insulin-sensitizing agents on the above-mentioned components of this metabolic syndrome. METHODS: Experimental metabolic syndrome was induced in Sprague-Dawley rats by feeding them a fructose-enriched diet (FED) for 5 weeks. During the last 2 weeks, the rats were treated with amlodipine, captopril, bezafibrate, or rosiglitazone in addition to FED. The control group did not receive any medication. Another control group was fed standard rat chow for 5 weeks. Post- and pretreatment measurements of body weight, systolic blood pressure (SBP), fasting plasma insulin, triglycerides, and total homocysteine concentrations were compared. RESULTS: Amlodipine reduced SBP but did not show metabolic impact. Bezafibrate improved SBP, triglycerides, and insulin but induced elevation of homocysteine levels. Captopril and rosiglitazone remarkably improved SBP, insulin, triglycerides, and total homocysteine levels. In addition, rosiglitazone alone promoted weight gain. CONCLUSIONS: The results indicate that captopril and rosiglitazone have a greater cardiovascular protective potential than amlodipine or bezafibrate. Captopril would be the best choice for patients with metabolic syndrome in whom hypertension and obesity are prominent, whereas rosiglitazone would be the preferred drug when glucose and other metabolic parameters are disturbed.

Clinical significance of renal function in hypertensive patients at high risk: results from the INSIGHT trial.

BACKGROUND: Increasing evidence suggests renal involvement in hypertension-related cardiovascular and cerebrovascular complications. To assess this role of renal function in more detail, we studied the evolution of renal function and the relationship of renal function with mortality and morbidity in the Intervention as a Goal in Hypertension Treatment (INSIGHT) study. METHODS: The INSIGHT study was a double-blind, randomized, multicenter trial in patients with hypertension and at least 1 additional cardiovascular risk factor. Treatment consisted of nifedipine gastrointestinal therapeutic system, 30 mg/d, or hydrochlorothiazide-amiloride (25 mg/d of hydrochlorothiazide and 2.5 mg/d of amiloride hydrochloride). Primary outcome was a composite of cardiovascular death, myocardial infarction, heart failure, and stroke. Renal function was assessed by measuring creatinine clearance, serum creatinine level, and serum uric acid level and by the presence of proteinuria. RESULTS: Creatinine clearance fell more in nifedipine recipients than in hydrochlorothiazide-amiloride recipients. Renal insufficiency developed in 2% of nifedipine recipients and 5% of hydrochlorothiazide-amiloride recipients. Primary outcomes occurred in 15% of patients with increased serum creatinine levels and 6% of patients with normal levels (odds ratio [OR] 2.89; 95% confidence interval [CI], 1.92-4.36; P<.001). Primary outcomes were more likely in patients with low creatinine clearance (<60 mL/min) than in those with higher clearances (9% vs 5%, respectively [OR, 1.51, 95%CI, 1.22-1.88; P<.001]). CONCLUSIONS: Renal function is an important predictor of risk in hypertensive patients at high risk. Antihypertensive treatment with a long-acting dihydropyridine calcium channel blocker may better preserve renal function than would treatment with diuretics.

Screening for hypertension in high school.

Arterial hypertension is a major risk factor for atherosclerotic ischemic heart disease and cerebrovascular stroke. Blood pressure measurements were taken in the supine position in 6,282 healthy adolescents (3073 boys, 3209 girls) aged 13-17 years of both sexes. Forty-eight subjects were found to have hypertension: 35 idopathic and 13 secondary to reflux nephropathy, chronic glomerulonephritis, coarctation of the aorta, and hemolytic uremic syndrome. Systolic blood pressure was significantly higher among males than females at ages 15-17 years (p<0.001); diastolic blood pressure was higher among males at age 17 years only (p<0.05). Males with BMI>17 exhibited higher systolic blood pressure than females. Prevalence of hypertension, mostly primary, in a large cohort of students was 0.76%. Early screening is important for early interventions and reducing cardiovascular morbidity and mortality in adulthood.

The Framingham prediction rule is not valid in a European population of treated hypertensive patients.

BACKGROUND: Stratification of population groups according to cardiovascular risk level is recommended for primary prevention. OBJECTIVE: To assess whether the Framingham models could accurately predict the absolute risk of coronary heart disease (CHD) and stroke in a large cohort of middle-aged European patients with hypertension, and rank individual patients according to actual risk. DESIGN: A prospective cohort study comparing the actual risk with that predicted by either the Framingham equations or models derived from the INSIGHT study. PATIENTS AND SETTING: From the INSIGHT prospective trial, conducted in eight countries of Western Europe and Israel, we selected 4407 European patients younger than 75 years without previous cardiovascular events. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Major cardiovascular events. RESULTS: In this population (45% men, mean age 64.1 years), 124 (2.8%) patients had CHD and 96 (2.2%) had strokes after a median follow-up of 3.7 years. Overestimation of absolute CHD risk by the Framingham equation was observed in all countries (from 2% in the UK to 7% in France), whereas predicted risk of stroke was close to the actual risk. However, patients in the highest risk quintile within each country had a threefold greater risk of a cardiovascular event than those in the lowest quintile. CONCLUSIONS: The Framingham models should not be used to predict absolute CHD risk in the European population as a whole. However, these models may be used within each country, provided that cut-off points defining high-risk patients have been determined within each country.

Drug therapy of renovascular hypertension.

The renin-angiotensin system is responsible for renovascular hypertension resulting from narrowing of the renal arteries. Inhibitors of angiotensin-converting enzyme (ACE) interrupt the conversion of angiotensin I to angiotensin II, causing a reduction in blood pressure. Several drugs of this family have been introduced since captopril was launched, including enalapril, lisinopril, ramipril and others. While they are effective antihypertensive agents, they can in some cases lead to deterioration of renal function, especially in patients with bilateral renal artery stenosis or stenosis of a solitary kidney. ACE inhibitors must also be administered with caution to sodium-depleted patients. Calcium antagonists, presumed to be ideal for the treatment of low renin hypertension, have also proved to be effective in patients with renal artery stenosis, many of whom have severe refractory hypertension. These agents, in common with ACE inhibitors, may be useful for determining the lateralisation index used to establish the kidney responsible for hypertension.

Trandolapril and endothelin antagonist LU-135252 in the treatment of the fructose-induced hypertensive, hyperinsulinemic, hypertriglyceridemic rat.

BACKGROUND: In view of the demonstrated interaction between endothelin and the renin-angiotensin system, the antihypertensive effect of combined therapy with an endothelin antagonist LU-135252 and the angiotensin converting enzyme inhibitor trandolapril, was studied in fructose-induced hypertensive, hyperinsulinemic, hypertriglyceridemic male Sprague-Dawley rats. METHODS: Forty animals were fed a fructose-enriched diet (Tekled, Harlan) for 5 weeks, as follows: group A, fructose only; group B, trandolapril 0.1 mg/kg/day added during the last 2 weeks; group C, LU-135252 100 mg/kg/day added during the last 2 weeks; group D, both trandolapril and LU-135252 added the last 2 weeks. Systolic blood pressure (BP) was measured weekly in conscious rats by the indirect tail-cuff method. Blood samples from a retro-orbital sinus puncture were taken at the beginning of the experiment and after 3 and 5 weeks and examined for insulin and triglyceride concentrations. RESULTS: Systolic BP decreased in group B (trandolapril) from 148.8 +/- 9.8 at 3 weeks to 138.3 +/- 8.7 mm Hg after 5 weeks; in group C (endothelin antagonist) from 155.1 +/- 5.5 to 142.5 +/- 10.6 mm Hg; and in group D (combination) from 154.6 +/- 10.9 to 121.2 +/- 8.9 mm Hg. Triglyceride levels decreased only in the combined trandolapril/endothelin antagonist group from 167.6 +/- 55.3 in the third week to 134.9 +/- 53.7 mg/dL after 5 weeks. Insulin levels decreased only on combination therapy from 7.4 +/- 3.6 to 5.3 +/- 3.8 ng/mL during the same period. The BP decrease was additive compared with the respective individual substances. CONCLUSIONS: The trandolapril/endothelin antagonist combination appears to offer a rational antihypertensive combination that is superior to that of either drug alone. This finding applies to the specific rat model studied in which BP, insulin, and triglycerides were increased by fructose diet.

Oxidative stress in hypertensive,diabetic, and diabetic hypertensive rats.

BACKGROUND: Reactive oxygen species play a key role in the formation of endothelial dysfunction accompanying diabetes mellitus, hypertension, and other cardiovascular diseases. METHOD: This study compares oxidative stress (OS) in Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR), non-insulin-dependent Cohen Diabetic rats (CDR), and Cohen Rosenthal diabetic hypertensive rats (CRDH), a unique animal model of both diabetes and hypertension. The OS was evaluated with a newly developed thermochemiluminiscence (TCL) analyzer (Lumitest Ltd., Nesher, Israel) that measures the oxidizability (ie, susceptibility to oxidation) of a test sample. RESULTS: The TCL oxidizability test results of sera from the different rats groups showed a time-dependent increase in TCL of up to 145% +/- 7% for WKY, 160% +/- 8% for SHR, 179% +/- 12% for CDR, and 226% +/- 15% for CRDH. These results were significant: P <.001 for SHR and CDR and P <.0001 for CRDH in comparison to WKY. Lipid peroxide levels also increased in each strain of rats: to 80 +/- 7.8 nmol/mL in WKY, 104 +/- 10.1 nmol/mL in SHR, 110 +/- 9.4 nmol/mL in CDR, and 167 +/- 11.7 nmol/mL in CRDH. These results were also significant: P <.001 for SHR, CDR and CRDH in comparison to WKY. CONCLUSION: The combination of hypertension and diabetes is accompanied by higher oxidative stress than that seen with either disorder alone.