Oxidative stress and hyperinsulinaemia in essential hypertension: different facets of increased risk.

OBJECTIVE: To evaluate oxidative stress markers in normo- and hyperinsulinaemic essential hypertension patients, and to relate these parameters to plasma glucose and insulin levels. METHODS: Diene conjugates, thiobarbituric acid reactive substances, iron-stimulated thiobarbituric acid reactive substances and anti-oxidative capacity of serum were detected in 32 untreated essential hypertension patients with normal glucose tolerance, divided into hyperinsulinaemic (n = 12, fasting plasma insulin level > 13.5 mU/l, means 2 SD of controls) and normo-insulinaemic (n = 20) subgroups, compared with 26 age- and body mass index-matched controls. Plasma glucose and insulin levels were measured during an oral glucose tolerance test. RESULTS: Levels of lipid peroxidation products (diene conjugates, thiobarbituric acid reactive substances and iron-stimulated thiobarbituric acid reactive substances) were elevated and serum anti-oxidative capacity decreased both in hyper- and in normo-insulinaemic patients compared with those in controls, with no significant differences between the hypertensive subgroups. No independent correlations were detected between oxidative stress markers and fasting or stimulated plasma insulin and glucose levels. The essential hypertension patients were characterized by a lower fasting glucose: insulin ratio and enhanced plasma insulin response to oral glucose test compared with controls. CONCLUSIONS: The results suggest that oxidative stress occurs, in addition to disturbances in glucose metabolism, in essential hypertension patients, thus potentially exposing them to increased risk of developing complications. Factors other than plasma insulin level are likely to contribute to oxidative stress in hypertensive patients with normal glucose tolerance.

Fibrinogen and the albumin-globulin ratio in essential hypertension: relations to plasma renin system activity.

The present study was designed to evaluate the blood albumin-globulin ratio and fibrinogen levels in untreated patients with essential hypertension according to their renin profile, and to investigate the relationship between these hemorheologic variables and metabolic cardiovascular risk factors. Patients with uncomplicated essential hypertension (n = 36, DBP = 95-115 mm Hg) were studied. Normotensive, age and sex matched volunteers (n = 19) served as controls. Assessment of plasma renin activity (PRA) related to concurrent 24 h sodium excretion was used to define patients with high (n = 12), medium (n = 16) and low renin profile (n = 8). Plasma fibrinogen levels and the albumin-globulin ratio (A-G ratio) were determined. The A-G ratio was significantly lower (P < 0.05) in the high PRA group compared to the low renin group or the controls. The A-G ratio was significantly negatively related to PRA (r = -0.348; P = 0.043) and serum C-peptide (r = -0.395; P = 0.017). Fibrinogen levels were lower (P < 0.05) in the controls when compared to high and medium PRA group. Fibrinogen was associated with total cholesterol (r = 0.479; P = 0.037), HDL cholesterol (r = -0.467; P = 0.028), plasma triglycerides (r = 0.414; P = 0.012) and fasting plasma glucose level (r = 0.358; P = 0.032). In conclusion, essential hypertensive patients with high PRA display more pronounced alterations in blood proteins, particularly in the decrease of the A-G ratio than patients with low PRA. This may be one additional factor accounting for the higher incidence of cardiovascular disease previously reported in high PRA group.

Antihypertensive and renal effects of isradipine in essential hypertension: focus on renin system activity.

Calcium antagonists are known to exert various effects on the kidney that might modulate their antihypertensive potential. This study evaluated the renal effects, along with the efficacy, of isradipine in two subgroups of patients with mild to moderate essential hypertension (EH), defined according to plasma renin activity (PRA). Twenty-six patients were randomly assigned to receive 12-week treatment with slow-release isradipine (2.5-5 mg) or placebo. Assessment of PRA related to concurrent 24-hour sodium excretion was used to define patients with high/medium (n=16) and low renin profile (n=10). Urinary albumin excretion (UAE), serum creatinine and glomerular filtration rate (GFR, as endogenous creatinine clearance) were measured. Blood pressure (BP) decrease with isradipine was greater in the low PRA group as compared with the high/medium PRA group (P<0.05), and normalization of BP was achieved in all low-renin patients compared with 57% in the high/medium PRA group. BP reduction in the placebo group was statistically not significant. Isradipine, but not placebo, induced significant reduction in UAE (P<0.05); the decrease was similar in both PRA groups. Treatment did not cause any significant changes in GFR, PRA, urinary sodium or creatinine excretion, or serum aldosterone or creatinine concentrations. The decrease of BP in the whole isradipine-treated group was inversely correlated with pretreatment serum creatinine as well as with basal urinary creatinine excretion. In conclusion, the antihypertensive effect of isradipine was more pronounced in low-renin EH patients, despite similar effects on renal function and UAE in both PRA groups.

The renin-angiotensin system in essential hypertension: associations with cardiovascular risk.

The importance of the renin-angiotensin system (RAS) in blood pressure regulation is well established. High RAS activity has also been implicated in connection with elevated cardiovascular risk in patients with essential hypertension. Data from epidemiological studies have related high plasma renin levels in essential hypertensive patients to cardiovascular complications. However, whether renin itself is a risk factor of cardiovascular events or just acts as a marker for other risk factors still remains to be elucidated. Several possible mechanisms that could be responsible for the association between elevated RAS activity and cardiovascular risk are reviewed. The concept of high RAS activity being a cardiovascular risk factor is strongly supported by results from large clinical studies showing the beneficial effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in congestive heart failure and hypertension. Knowing more about the exact mechanisms of the association between high RAS activity and cardiovascular complications would enable us to profile the treatment of high blood pressure more specifically to improve outcome in individuals or groups of patients.

Association between plasma renin activity and metabolic cardiovascular risk factors in essential hypertension.

OBJECTIVES: To study the relationships between plasma renin activity and metabolic cardiovascular risk factors in patients with essential hypertension. SUBJECTS AND DESIGN: Patients with uncomplicated essential hypertension (n = 36) with a diastolic blood pressure of 95-115 mmHg were studied. Assessment of plasma renin activity (PRA) related to urinary sodium excretion was used to define subgroups with high (n = 12), medium (n = 16) and low renin profiles (n = 8). MAIN OUTCOME MEASURES: Fasting plasma lipid levels were determined. Glucose, insulin and C-peptide responses to standard oral glucose tolerance test (OGTT) were measured. RESULTS: Patients with high PRA had higher levels of plasma cholesterol (6.13 +/- 0.81 versus 4.67 +/- 0.7 mmol L-1, P < 0.05) and triglycerides (2.14 +/- 0.18 versus 0.98 +/- 0.13 mmol L-1, P < 0.05), than the low PRA group. HDL-cholesterol levels were lower in the high renin group than in the low renin group (1.05 +/- 0.04 versus 1.26 +/- 0.09 mmol L-1, P < 0.05). Insulin and C-peptide sums were higher in high PRA group (33.8 +/- 1.2 versus 25.1 +/- 0.9 and 2.6 +/- 0.3 versus 1.9 +/- 0.4 ng L-1, P < 0.05), than in the low PRA group. CONCLUSIONS: Essential hypertensive patients with a high renin profile display more pronounced dyslipidaemia and higher levels of plasma insulin than patients with a low renin profile. This may be one explanation for higher incidence of cardiovascular disease previously reported in high PRA group.

Evidence for oxidative stress in essential hypertension: perspective for antioxidant therapy.

BACKGROUND: Despite therapy, arterial hypertension continues to be a risk factor of coronary artery disease (CAD). The role of oxidative stress, an important source of vascular injury, in the genesis of this increased risk also needs to be defined, because several antihypertensive drugs have demonstrated antioxidant effects. This study tested the existence of oxidative stress in young (< 40 years) untreated patients with uncomplicated essential hypertension (EH). METHODS: Lipid peroxidation (LP) products (diene conjugates, basal and Fe-stimulated levels of thiobarbituric acid reactive substances) were detected spectrophotometrically in serum together with markers of antioxidant status (serum antioxidative capacity (AOC), red blood cell (RBC) glutathione) in 32 patients with mild-to-moderate EH and in 26 matched normotensive controls. RESULTS: All LP products were elevated (P < 0.01), while serum AOC was decreased (P < 0.001) and RBC glutathione increased (P < 0.05) in EH patients compared with controls. The presence of hypercholesterolaemia was not found to influence the differences in the measured parameters between hypertensive patients and controls significantly. CONCLUSIONS: The results indicate that oxidative stress occurs in young patients with uncomplicated EH. Therefore antihypertensive treatment; especially in patients whose vascular disease is still reversible, should provide antioxidant protection.