Improved insulin sensitivity by the angiotensin II-receptor blocker losartan is not explained by adipokines, inflammatory markers, or whole blood viscosity.

We have previously found improved insulin sensitivity after antihypertensive treatment with an angiotensin II-receptor blocker as compared with a calcium channel blocker in hypertensives. In this study, we compare the effect of these 2 principal different vasodilating agents on levels of adipokines, inflammatory variables, and whole blood viscosity in the same hypertensive patients with cardiovascular risk factors. We test whether potential differences in these variables might explain the difference seen in insulin sensitivity. Twenty-one hypertensive patients (11 women, 10 men) with mean age of 58.6 years and blood pressure of 160 +/- 3/96 +/- 2 mm Hg entered a 4-week run-in period with open-label amlodipine 5 mg. Thereafter, they were randomized double-blindly to additional treatment with amlodipine 5 mg or losartan 100 mg; and after 8 weeks of treatment, all patients underwent laboratory testing. After a 4-week washout phase with open-label treatment, the participants were crossed over to the opposite treatment regimen for 8 weeks before final examination. No significant differences were seen in the blood levels of adiponectin (7814 +/- 870 vs 8090 +/- 967 ng/mL), leptin (961 +/- 122 vs 965 +/- 147 pmol/L), resistin (11.7 +/- 1.0 vs 11.3 +/- 0.7 ng/mL), plasminogen activator inhibitor 1 activity (23.9 +/- 2.2 vs 25.1 +/- 2.2 U/mL), tumor necrosis factor alpha (1.35 +/- 0.11 vs 1.72 +/- 0.28 pg/mL), and high-sensitivity C-reactive protein (3.09 +/- 0.84 vs 2.09 +/- 0.42 mg/L) between treatment with amlodipine 10 mg or losartan 100 mg + amlodipine 5 mg, respectively. Although no significant differences in whole blood viscosity and blood pressure were observed between the 2 treatment regimens, a consistent trend toward lower viscosity was found at all shear rates as vasodilatory treatment was intensified (baseline to amlodipine 5 mg to amlodipine 10 mg to losartan 100 mg + amlodipine 5 mg). Our data do not support that effects on adipokines, inflammatory markers, and whole blood viscosity could explain improved insulin sensitivity seen on AT1-receptor blockade.

The effect of losartan versus atenolol on cardiovascular morbidity and mortality in patients with hypertension taking aspirin: the Losartan Intervention for Endpoint Reduction in hypertension (LIFE) study.

OBJECTIVES: We conducted a subgroup analysis in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study to determine whether aspirin interacted with the properties of losartan, an angiotensin-II receptor antagonist. BACKGROUND: Negative interactions between angiotensin-converting enzyme inhibitors and aspirin have been reported. There are no data reported from clinical trials about possible interactions between angiotensin-II receptor antagonists and aspirin. METHODS: The LIFE study assigned 9,193 patients with hypertension and left ventricular hypertrophy (LVH) to losartan- or atenolol-based therapy for a mean of 4.7 years, with 1,970 (21.4%) taking aspirin at baseline. The primary composite end point (CEP) included cardiovascular death, stroke, and myocardial infarction (MI). The present cohort was stratified by aspirin use at baseline. RESULTS: Blood pressures were reduced similarly in the losartan with aspirin (n = 1,004) and atenolol with aspirin (n = 966) groups. The CEP was reduced by 32% (95% confidence interval 0.55 to 0.86, p = 0.001) with losartan with aspirin compared to atenolol with aspirin, adjusted for Framingham risk score and LVH. The test for treatment versus aspirin interaction, excluding other covariates, was significant for the CEP (p = 0.016) and MI (p = 0.037). CONCLUSIONS: There was a statistical interaction between treatment and aspirin in the LIFE study, with significantly greater reductions for the CEP and MI with losartan in patients using aspirin than in patients not using aspirin at baseline. Further studies are needed to clarify whether this represents a pharmacologic interaction or a selection by aspirin use of patients more likely to respond to losartan treatment.

Adrenal medullary overactivity in lean, borderline hypertensive young men.

BACKGROUND: There may be a link among stress, adrenal medullary activation, and the development of hypertension. Obesity is characterized by sympathetic activation and predisposes to hypertension, but may be associated with low or normal adrenal medullary activity. We hypothesized that plasma epinephrine (E) levels and adrenal medullary responsiveness to mental stress are lower in overweight than in lean borderline hypertensive subjects. METHODS: We compared groups of lean (n = 62) and overweight (n = 29) borderline hypertensive young men as well as lean (n = 36) and overweight (n = 7) normotensive young men from the same population. Plasma catecholamines and heart rate (HR) were measured at rest during a hyperinsulinemic glucose clamp and during mental arithmetic-induced stress. RESULTS: Plasma norepinephrine (NE) and E, HR, and responses to stress were increased in borderline hypertensive subjects. Our results showed that NE was increased only in lean borderline hypertensive subjects at rest, but in overweight subjects as well during stress, with DeltaNE being similar in lean and overweight subjects. We found that E was higher in lean than in overweight borderline hypertensive subjects at rest and during stress (both P <.001), as were DeltaE and DeltaHR (both P <.05). Independent of BP status, body mass index was negatively related to E during stress (P <.01) and waist circumference negatively related to resting E (P <.001) and DeltaHR (P =.02). CONCLUSIONS: Sympathetic neural activity and responsiveness are increased in borderline hypertensive young men, but measures of overweight are independently related to lower plasma E and HR responses. We suggest that adrenal medullary activation in borderline hypertension mainly characterizes lean subjects.

High screening blood pressure is related to sympathetic nervous system activity and insulin resistance in healthy young men.

The cardiovascular metabolic syndrome is characterized by the presence of several cardiovascular risk factors, including blood pressure (BP) elevation. We aimed to study the relation between mental stress, plasma catecholamines, BP and BP responses to mental stress in healthy young Caucasian men selected from different levels of screening BP. We included 98 men with high and 22 men with normal screening BP. They were examined at baseline in the laboratory, during a hyperinsulinemic, isoglycemic glucose clamp and during mental stress. At baseline in the laboratory, the men with high screening BP were characterized by elevated BP (p < 0.005) and plasma catecholamines (p < 0.05), but unaltered serum lipid levels compared to men with normal screening BP. After 2 h rest the differences almost disappeared, but could be reproduced during a mental arithmetic stress test. The men with elevated screening BP had significantly higher fasting glucose (p = 0.01) and lower insulin sensitivity (p < 0.005). In a multiple regression model, norepinephrine during mental stress (R2 = 0.10, p < 0.05) was the main variable to retrospectively explain allocation to the normal or high screening BP group. In conclusion, young healthy men with elevated screening BP are characterized by increased sympathetic activity and insulin resistance. Norepinephrine during mental stress is the main variable to explain allocation to the normal or elevated screening BP group. We have shown that one single screening BP measurement predicts insulin resistance and elevated fasting glucose in this cohort.