Effects of Angiotensin‐Converting Enzyme Inhibition on Leptin and Adiponectin Levels in Essential Hypertension

Abstract

Activation of the renin-angiotensin-aldosterone system (RAAS) and abnormal adipokine levels are biological alterations that affect blood pressure regulation and interact to link hypertension, obesity and metabolic diseases. While imbalanced levels of hormones produced by adipocytes including hypo-adiponectinaemia and hyperleptinaemia were reported in hypertension, little is known about how antihypertensive therapy affects these alterations. This study aimed to evaluate the effects of enalapril on plasma adiponectin and leptin levels in hypertensive individuals. Thirty-seven untreated hypertensive patients were prospectively treated with enalapril for 8 weeks. Blood samples were collected at baseline and after the treatment with enalapril. Plasma adiponectin and leptin levels were measured by enzyme-linked immunoassay. We found significant increases in adiponectin levels after enalapril treatment (5.4 AE 3.7 versus 6.0 AE 4.5 lg/mL, meanAES.D., p = 0.04). Conversely, leptin levels were unchanged (18.0 AE 14.7 versus 18.4 AE 14.8 ng/mL, mean AE S.D., p = 0.31). Multiple linear regression revealed that baseline leptin is a significant predictor of systolic blood pressure reduction (b=0.269, p = 0.01) in hypertensive individuals treated with enalapril. While enalapril increases adiponectin levels in hypertensive individuals, baseline leptin levels predict blood pressure reduction in response to this therapy. These findings support the idea of an important relationship between RAAS and adipose tissue in hypertension and suggest that enalapril improves the adipokine profile, possibly allowing beneficial effects to overweight or obese hypertensive individuals.Hypertension, obesity and metabolic abnormalities share common physiopathological mechanisms including activation of the renin-angiotensin-aldosterone system (RAAS) and alterations in adipokine levels [1]. Adiponectin and leptin are hormones produced by adipocytes [2] and imbalanced levels of these hormones have been shown in hypertensive patients compared with normotensive controls [3]. An inverse relationship between adiponectin and blood pressure (BP) levels was reported, and hypo-adiponectinaemia has been suggested as a risk factor for hypertension [3]. The cardiovascular protective effects of adiponectin are mediated by anti-inflammatory, insulin-sensitizing and antiatherogenic mechanisms [4][5][6]. On the other hand, hyperleptinaemia promotes cardiovascular remodelling [7,8] mainly by increasing sympathetic nervous system activity [9]. Indeed, increased leptin levels may predict development of hypertension, independent of BMI and insulin resistance [10].Increasing evidence suggests that RAAS and adipose tissue are interplayers in BP regulation [11][12][13]. It has been suggested that angiotensin-converting enzyme inhibitors (ACEi) may offer advantages as monotherapy in the treatment of obese hypertensive individuals, particularly in the prevention of metabolic disorders [14]. Moreover, some studies demonstrated that drug interfering with RAAS can i...

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“…In this context, pharmacologic strategies to regulate adipokines levels seem to be of great clinical interest since they may implicate benefits on preventing cardiovascular and metabolic disorders. Drugs that interfere with RAAS (angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers) have been reported to improve the adipokine profile in hypertensive individuals . Moreover, MR blockade improves expression of adiponectin and reduces expression of proinflammatory factors, reversing obesity‐related changes .…”

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