Leptin is a 16-kDa peptide hormone that is primarily synthesized and secreted by adipose tissue. One of the major actions of this hormone is the control of energy balance by binding to receptors in the hypothalamus, leading to reduction in food intake, elevation in temperature and energy expenditure. In addition, increasing evidence suggests that leptin, through both direct and indirect mechanisms, may play an important role in cardiovascular and renal regulation. Although the relevance of endogenous leptin needs further clarification, it appears to function as a pressure- and volume-regulating factor under conditions of health. However, in abnormal situations characterized by chronic hyperleptinemia such as obesity, it may function pathophysiologically for the development of hypertension and possibly also for direct renal, vascular and cardiac damage.

This review focuses on recent human studies with the angiotensin-converting enzyme (ACE) inhibitor enalapril, prescribed either alone or in combination with a diuretic, to patients with essential hypertension and to patients with hypertension associated with moderate to severe renal parenchymal disease. Data suggest that enalapril therapy may provide a renal protective effect. In addition to lowering and controlling systemic arterial blood pressure, enalapril therapy is associated with stabilisation of, and/or improvement in effective renal plasma flow, glomerular filtration rate (GFR) and urinary protein excretion. Such renal protective effects are probably mediated by normalisation of both the systemic arterial blood pressure and intraglomerular capillary hydraulic pressure, and by an increase in the glomerular ultrafiltration coefficient. Drug therapy enabling control of both systemic and glomerular hypertension may prevent hypertensive renal end-organ damage and attenuate the natural progression of renal parenchymal disease.

Leptin is a 16-kDa-peptide hormone that is primarily synthesized and secreted by adipose tissue. One of the major actions of this hormone is the control of energy balance by binding to receptors in the hypothalamus, leading to reduction in food intake and elevation in temperature and energy expenditure. In addition, increasing evidence suggests that leptin, through both direct and indirect mechanisms, may play an important role in cardiovascular and renal regulation. While the relevance of endogenous leptin needs further clarification, it appears to function as a pressure and volume-regulating factor under conditions of health. However, in abnormal situations characterized by chronic hyperleptinemia such as obesity, it may function pathophysiologically for the development of hypertension and possibly also for direct renal, vascular, and cardiac damage.

PURPOSE OF REVIEW:Adipose tissue is now considered to be an active physiologic system operating in concert with multiple other organs. Leptin is a peptide hormone that is primarily synthesized and secreted by adipose tissue whose principal action is the control of appetite and energy balance. However, current information suggests that leptin exerts pleiotropic effects on several organ systems. Herein, we review the potential role of leptin in cardiovascular and renal physiological conditions as well as pathophysiological situations including obesity and hypertension.RECENT FINDINGS:Increasing evidence suggests that leptin may function as a pressure and volume-regulating factor under conditions of health; however, in situations characterized by chronic hyperleptinemia such as obesity, it may function pathophysiologically for the development of hypertension and possibly also for adverse renal, vascular and cardiac remodeling.SUMMARY:Adipose tissue should be regarded as a potentially important mediator of cardiorenal physiology. Further research awaits the characterization of additional mechanisms of action of leptin, including its interface with other important endocrine and hemodynamic sodium-volume regulatory systems, in both health and disease, particularly in obesity and related comorbidities. This information could lead to the development of leptin analogues as well as leptin receptor blockers that given specific circumstances could optimize the beneficial actions of the hormone and minimize its deleterious effects.

The incidence and prevalence of obesity and the metabolic syndrome have risen markedly in the past decade, representing a serious cardiovascular health hazard with significant morbidity and mortality. The etiology of the metabolic syndrome and its various pathogenic mechanisms are incompletely defined and under intense investigation. Contemporary research suggests that the adipocyte-derived hormone leptin may be an important factor linking obesity, the metabolic syndrome, and cardiovascular disorders. Although recent evidence indicates that under normal conditions leptin may be an important factor in regulating pressure and volume, during situations of chronic hyperleptinemia and leptin resistance, this hormone may function pathophysiologically for the development of hypertension and cardiac and renal diseases. Future research will determine if reduction of circulating leptin and/or blockade of its peripheral actions can confer cardiovascular and renal protection in hyperleptinemic patients with obesity and the metabolic syndrome.

The incidence and prevalence of obesity has risen markedly in the last decade, and this epidemic represents a serious health hazard with significant morbidity and mortality. Although hypertension is recognized as one of the most serious consequences of obesity, its pathophysiology remains incompletely understood. Contemporary research suggests that the recently discovered hormone leptin may represent a common link between these 2 pathologic conditions. Leptin is primarily synthesized and secreted by adipocytes. One of the major functions of this hormone is the control of energy balance. By binding to receptors in the hypothalamus, it reduces food intake and promotes elevation in temperature and energy expenditure. In addition, increasing evidence suggests that leptin, through both direct and indirect actions, may play an important role in cardiovascular and renal functions. Although the relevance of endogenous leptin needs further clarification for the control of renal sodium excretion and vascular tone, it appears to be a potential pressure and volume-regulating factor in normal situations. However, in conditions of chronic hyperleptinemia, such as obesity, leptin may function pathophysiologically for the development of hypertension as well as cardiac and renal disease. Thus, in addition to weight control, reduction of circulating leptin may confer cardiovascular and renal protective effects in patients with obesity-hypertension.

Previous investigations in normotensive animals have demonstrated a marked natriuretic and diuretic response following the acute administration of supraphysiologic doses of synthetic leptin. However, the importance of endogenous leptin in the regulation of renal sodium and water balance is not yet defined. This study examined the hemodynamic and renal excretory effects of circulating leptin blockade with a specific polyclonal antibody in groups of normotensive, chronically saline-loaded Sprague-Dawley rats. In the experimental group (n = 10), leptin antibody significantly decreased urinary sodium excretion and urinary flow by approximately 30% compared to the control rats (n = 10). Mean arterial pressure remained unchanged. Collectively, these results are interpreted to suggest that leptin is an important renal sodium-regulating factor under conditions of mild sodium and volume expansion.

Leptin is a recently isolated circulating peptide hormone that is primarily synthesized and secreted by adipocytes. One of the major functions of this hormone is the control of energy balance by binding to receptors in the hypothalamus, leading to reduction in food intake, elevation in temperature and energy expenditure. In addition, increasing evidence suggests that leptin, through both direct and indirect actions, may play an important role in cardiovascular and renal functions. While the relevance of endogenous leptin needs further clarification, it appears to be a potential pressure- and volume-regulating factor, and may function pathophysiologically as a common link to obesity and hypertension.

Leptin is a circulating polypeptide hormone produced by an adipocyte-specific gene. It regulates energy balance by binding to receptors in the hypothalamus, leading to alterations in food intake, temperature, and energy expenditure. More recent pharmacologic information suggests that this circulating hormone may play an important role in the regulation of body fluid volume and pressures through direct and indirect actions. Although the relevance of the endogenous leptin on cardiovascular and renal function is yet to be clearly determined, it seems to be a potential salt-regulating factor and may function pathophysiologically as a common link to obesity and hypertension.

Leptin is a recently isolated circulating peptide hormone that is primarily synthesized and secreted by the adipocytes. A major function of this hormone is the control of energy balance by binding to receptors in the hypothalamus, leading to reduction in food intake, as well as elevation in temperature and energy expenditure. In addition, increasing pharmacological evidence suggests that leptin, through its direct and indirect actions, may play an important role in cardiovascular and renal functions. While the relevance of endogenous leptin needs further clarification, it appears to be a potential pressure and volume regulating factor, and may function pathophysiological as a common link to obesity and hypertension.

Mammalian hearts contain a family of peptides with potent natriuretic, diuretic, and vasorelaxant actions. In addition to atrial natruretic peptide (ANP) and brain natriuretic peptide, recent studies in humans and animals have suggested that the N-terminal ANP prohormone fragment 31-67 may represent another adaptive mechanism to achieve body fluid homeostasis. Furthermore, these investigations have also suggested that via different mechanisms of action on target organisms, the C-terminal hormone ANP 99-126 and pro-ANP 31-67 may coordinate and contribute to the regulation of hemodynamic and renal function in pathophysiologic situations, such as heart failure.

Calcium-channel blockers administered prior to and/or immediately following renal transplantation have been reported to attenuate the ischemic/reperfusion renal injury, to improve renal blood flow, and to decrease the incidence of delayed graft function. A prospective, randomized, double-blind, placebo-controlled study assessed the effect of a single oral dose of a long-acting calcium-channel blocker (nifedipine GITS 30 mg) on renal function and hemodynamics prior to the initiation of cyclosporine therapy in patients who underwent cadaveric renal transplantation. One week following renal transplantation, the nifedipine GITS-treated group had higher glomerular filtration rate (41 +/- 8 vs 23 +/- 5 mL/min/1.73 m(2) [SEM]) and effective renal plasma flow (244 +/- 37 vs 151 +/- 22 mL/min/1.73 m(2) [SEM]) compared with the placebo-treated group. No differences were noted between groups in:the need for hemodialysis. These data suggest that a single oral dose of a long-acting calcium-channel blocker, given prior to renal transplantation, shortens the renal recovery period.

It has been demonstrated previously that the atrial natriuretic factor prohormone fragment 31-67 (ProANF31-67) circulates in animals and possesses natriuretic and vasodilating actions. Although the plasma levels of the peptide are reportedly elevated in patients with high blood pressure, its role and actions in hypertension are unknown. In the present study, synthetic human ProANF31-67 was infused intravenously at doses of 0, 10, 30, and 100 ng/kg/min into respective groups of anesthetized normotensive and spontaneously hypertensive rats. Mean arterial pressure (MAP), urine flow rate (UV), and sodium excretion (UNaV) were measured during two consecutive 30-min periods. In both strains of rats, reductions in MAP with ProANF31-67 were similar in magnitude and dose-related. Sodium excretion responses to the peptide infusions also were remarkably similar in both normotensive and hypertensive rats, and the responses demonstrated 3- to 5-fold (P < 0.05) increments compared to control at the doses of 10 and 30 ng/kg/min. However, in the two strains of rats, attenuation of natriuresis occurred with the highest infusion dose of 100 ng/kg/min and was probably related to the large decreases in MAP of 17-23 mmHg at this dose of the peptide. The present results indicate the ProANF31-67 has important hemodynamic and renal effects in hypertension and may represent one compensatory mechanism involved in this disease.