Blockade of the Renin-Angiotensin System Increases Adiponectin Concentrations in Patients With Essential Hypertension

Abstract

Abstract-Adiponectin, an adipocyte-derived protein, has been suggested to play an important role in insulin sensitivity.We examined the association between insulin sensitivity (M value) evaluated by the euglycemic-hyperinsulinemic glucose clamp and adiponectin concentrations in 30 essential hypertensives (EHT) and 20 normotensives (NT) and investigated the effect of blockade of the renin-angiotensin system (RAS) on adiponectin concentrations. EHT were divided into 12 insulin-resistant EHT (EHT-R) and 18 non-insulin-resistant EHT (EHT-N) using meanϪ1 SD of the M value in NT. There were no intergroup differences in age, gender, and body mass index (BMI). EHT-R had significantly higher levels of insulin and triglyceride and lower levels of adiponectin than did NT and EHT-N. EHT-R had higher levels of free fatty acid and lower levels of high-density lipoprotein (HDL) cholesterol than did EHT-N. Adiponectin concentrations were positively correlated with M value and HDL cholesterol and negatively correlated with BMI, insulin, free fatty acid, and triglyceride but not with blood pressure. M value, BMI, and HDL cholesterol were independent determinants of adiponectin concentrations in multiple and stepwise regression analyses. Sixteen EHT were treated with an angiotensin-converting enzyme inhibitor (temocapril, 4 mg/d; nϭ9) or an angiotensin II receptor blocker (candesartan, 8 mg/d; nϭ7) for 2 weeks. Treatment with temocapril or candesartan significantly decreased blood pressure and increased M value and adiponectin concentrations but did not affect BMI and HDL cholesterol. These results suggest that hypoadiponectinemia is related to insulin resistance in essential hypertension and that RAS blockade increases adiponectin concentrations with improvement in insulin sensitivity.

Increased serum adiponectin levels in type 1 diabetic patients with microvascular complications

“…On the other hand, even after adjustment for differences in kidney function, serum ADPN remained elevated in patients with nephropathy compared with normoalbuminuric patients (Table 3). The study groups were also examined for differences in treatment with ACE inhibitors, because these drugs have been shown to increase serum ADPN in non-diabetic patients with essential hypertension [33], but as shown this did not explain our observations. Thus, there is evidence that mechanisms other than kidney function may be responsible for the higher serum ADPN levels in type 1 diabetic patients with nephropathy.…”

Potential impact of renin–angiotensin system inhibitors and calcium channel blockers on plasma high-molecular-weight adiponectin levels in hemodialysis patients

“…It has been reported that RAS inhibitors 25,26 and CCBs 27 increase adiponectin levels in non-hemodialysis patients. Previous studies have shown that angiotensin II receptor blocker inhibits obesity-induced hypoadiponectinemia through the inhibition of reactive oxygen species generation in mice 28 and that some angiotensin II receptor blockers have peroxisome proliferator-activated receptor g-activating properties, 29 thereby stimulating adiponectin production.…”

“…Huang et al 20 also investigated the effect of the RAS blockade and did not find any effect on adiponectin levels. However, several investigators reported that angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker 25,26 and CCB 27 increase adiponectin levels in non-hemodialysis patients. Thus, we speculated that these drugs might also increase adiponectin levels in hemodialysis patients.…”

Antihypertensive treatment, adiponectin and cardiovascular risk

“…Recent studies have explored the relationship between angiotensin II, the renin-angiotensin system and its blockade and adiponectin. [13][14][15][16][17] One study 13 in rats measured changes in plasma adiponectin levels following angiotensin II infusion and found that angiotensin II infusion decreased plasma adiponectin levels via the angiotensin II type I receptors, resulting in impaired insulin sensitivity.…”

“…Table 1 summarizes the findings of these studies. Furuhashi et al 14 reported a significant increase in adiponectin levels Nifedipine therapy improved platelet activation markers, micro particles and adiponectin levels in hypertensive patients with type II diabetes Six-month nifedipine therapy reduced blood pressure, with a significant rise in adiponectin levels in subjects with type II diabetes (Po0.01) Nifedipine has possible beneficial antiatherosclerotic effects in addition to its antihypertensive action Significant fall in the baseline high levels of procoagulant markers (platelet-and monocytederived microparticles) in hypertensives with diabetes with nifedipine therapy Abbreviations: ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; RAS, renin-angiotensin system.…”