normotensive African Americans, but once these individuals were adjusted for obesity, no significant relationship was further observed between leptin and blood pressure (El- Gharbawy et al 2002). In summary, it seems evident that serum leptin levels are significantly elevated in obese hypertensive individuals when compared with obese normotensives. However this relationship between leptin and blood pressure may not always be as evident after controlling for BMI in some subjects, making the assumption of leptin as a one of the potential causes of hypertension in obesity, less consistent. Possible treatment considerations The elevated leptin concentrations seen in obese hypertensive humans are mainly due to abdominal adipose tissue secretion. Current studies have elucidated that some antihypertensives might be more relevant than others in terms of reducing leptin levels in obesity. For example, angiotensin II has recently been found to stimulate leptin production in human adipose tissue (Skurk et al 2005), possibly by means of activation of the angiotensin II type 1 receptor subtype. This effect was completely abolished when the angiotensin receptor blocker (ARB) candesartan was employed prior to angiotensin II administration in human fat cells. In agreement with this observation, valsartan, anotherARB, aside from lowering blood pressure, decreased leptin levels and BMI in obese individuals, when compared with the calcium channel blocker (CCB) felodipine (Fogari et al 2005). Similarly, the angiotensin- converting enzyme (ACE) inhibitor, enalapril, in combination with a weight reduction program, evidenced the greatest benefits in terms of weigh loss and diminution of plasma norepinephrine, insulin, and leptin levels in comparison with control groups treated with weight reduction program alone or combined with the CCB amlodipine (Masuo et al 2001). In another study, the beta-blocker (BB) pindolol showed a marked suppressive effect on serum leptin levels, not seen in hypertensive individuals on perindopril, or felodipine (Ficek et al 2002). In contrast to these findings, Sonmez et al (2001) in an earlier study, found no clear effect of the ARB Losartan on leptin levels in young hypertensive individuals despite its hypotensive action. Likewise, both enalapril and clonidine reduced heart sympathetic activity and blood pressure in another clinical trial, but failed to decrease serum leptin levels in normotensive obese and non-obese subjects after 7 days of treatment (Amador et al 2004). Leptin and hypertension in obesity It is worth mentioning that obesity is associated with sodium retention and increased extracellular volume inducing hypervolemia and increased cardiac output, leading to the activation of the renin–angiotensin and sympathetic nervous system; all of these factors c o n t r i b u t i n g u l t i m a t e l y t o t h e d e v e l o p m e n t o f hypertension and eccentric-concentric left ventricular hypertrophy: changes that may induce congestive heart failure, arrhythmia, and sudden death (Figure 2) (Zhang and Reisin 2000). Although the studies are not yet consistent, it seems that pharmacologic suppression of the sympathetic nervous system, the renin–agiotensin system and, lately hyperleptinemia with ACE inhibitors, ARB and BB, may resemble the blood pressure reduction effect induced by weight loss. Diuretics, on the other hand, by eliminating urinary sodium and extracellular fluid, might also play a significant role in the treatment of hypertension in obesity, as these individuals are known for being sodium retainers and hypervolemics. Nevertheless, BBs and diuretics may affect insulin sensitivity and cause hyperglycemia and so their use should be carried out with close monitoring of glycemia in this patient population. Summary In summary, leptin the adipose tissue-derived hormone by way of distinct neurochemical pathways stimulates s y m p a t h e t i c n e r v e a c t i v i t y i n t h e r m o g e n i c a n d nonthermogenic tissue, affecting the metabolic and cardiovascular system respectively. Leptin, acutely, could have a dual influence on blood pressure control, in which the net effect would depend on the balance between the pressor action through activation of the sympathetic nervous system and a possible natriuretic and peripheral vasorelaxant effect of the hormone on the renal tubules and endothelium. In contrast, chronic hyperleptinemia may lead to abnormal renal sodium retention and vasoconstriction associated with renal sympathetic activation and NO deficiency, both contributing to pressure elevation in obese individuals, who may develop resistance to the satiety effect of leptin with preservation o f t h e c a r d i o v a s c u l a r e ff e c t . Tr e a t m e n t o f t h e s e individuals might be focused in overcoming the hemodynamic alterations seen in obesity, such as antinatriuresis and overactivity of the sympathetic and renin–angiotensin systems. Vascular Health and Risk Management 2006:2(2) 167