leptin and Hypertension--Renal

Several articles have dealt with the importance and mechanisms of the sympathetic nervous system alterations in experimental animal models of hypertension. This review addresses the role of the sympathetic nervous system in the pathophysiology and therapy of human hypertension. We first discuss the strengths and limitations of various techniques for assessing the sympathetic nervous system in humans, with a focus on heart rate, plasma norepinephrine, microneurographic recording of sympathetic nerve traffic, and measurements of radiolabeled norepinephrine spillover. We then examine the evidence supporting the importance of neuroadrenergic factors as promoters and amplifiers of human hypertension. We expand on the role of the sympathetic nervous system in 2 increasingly common forms of secondary hypertension, namely hypertension associated with obesity and with renal disease. With this background, we examine interventions of sympathetic deactivation as a mode of antihypertensive treatment. Particular emphasis is given to the background and results of recent therapeutic approaches based on carotid baroreceptor stimulation and radiofrequency ablation of the renal nerves.

Topics: Animals; Antihypertensive Agents; Clinical Trials as Topic; Diagnostic Techniques, Cardiovascular; Forecasting; Heart Rate; Humans; Hyperinsulinism; Hypertension; Hypertension, Renal; Insulin Resistance; Kidney; Kidney Diseases; Leptin; Melanocortins; Metabolic Syndrome; Multicenter Studies as Topic; Neuroimaging; Norepinephrine; Obesity; Sympathectomy; Sympathetic Fibers, Postganglionic; Sympathetic Nervous System; Vasoconstriction

Exposure to maternal obesity or a maternal diet rich in fat during development may have adverse outcomes in offspring, such as the development of obesity and hypertension. The present study examined the effect of a maternal high-fat diet (m-HFD) on offspring blood pressure and renal sympathetic nerve activity, responses to stress, and sensitivity to central administration of leptin and ghrelin. Offspring of New Zealand white rabbits fed a 13% HFD were slightly heavier than offspring from mothers fed a 4% maternal normal fat diet (P<0.05) but had 64% greater fat pad mass (P=0.015). Mean arterial pressure, heart rate, and renal sympathetic nerve activity at 4 months of age were 7%, 7%, and 24% greater, respectively (P<0.001), in m-HFD compared with maternal normal fat diet rabbits, and the renal sympathetic nerve activity response to airjet stress was enhanced in the m-HFD group. m-HFD offspring had markedly elevated pressor and renal sympathetic nerve activity responses to intracerebroventricular leptin (5-100 µg) and enhanced sympathetic responses to intracerebroventricular ghrelin (1-5 nmol). In contrast, there was resistance to the anorexic effects of intracerebroventricular leptin and less neuronal activation as detected by Fos immunohistochemistry in the arcuate (-57%; P<0.001) and paraventricular (-37%; P<0.05) nuclei of the hypothalamus in m-HFD offspring compared with maternal normal fat diet rabbits. We conclude that offspring from mothers consuming an HFD exhibit an adverse cardiovascular profile in adulthood because of altered central hypothalamic sensitivity to leptin and ghrelin.

Topics: Adiposity; Animals; Blood Pressure; Dietary Fats; Female; Ghrelin; Hypertension, Renal; Kidney; Leptin; Male; Organ Size; Pregnancy; Prenatal Exposure Delayed Effects; Rabbits; Stress, Physiological; Sympathetic Nervous System

To evaluate the relationship between metabolic syndrome (MetS) and the fasting serum leptin concentration in hemodialysis (HD) patients.. Fasting blood samples were obtained from 101 HD patients. MetS and its components were defined using the diagnostic criteria of the International Diabetes Federation.. Forty-eight patients (47.5%) had MetS. Serum leptin concentrations were positively correlated with MetS (p<0.001). Serum leptin levels correlated with increasing numbers of MetS criteria in HD patients (p=0.001). Univariate linear regression analysis showed that the pre-HD body weight (p<0.001), waist circumference (p<0.001), body mass index (p=0.001), triglycerides (p=0.003), insulin level (p=0.043), and homeostasis model assessment of insulin resistance (p=0.003) positively correlated with serum leptin levels in HD patients and high-density lipoprotein-cholesterol (p=0.016) negatively correlated with serum leptin levels in HD patients. Multivariate forward stepwise linear regression analysis of the significant variables revealed that pre-HD body weight (R(2)=0.175; p<0.001) was the independent predictor of the fasting serum leptin concentration.. Fasting serum leptin levels positively correlated with MetS and the pre-HD body weight could influence serum leptin in HD patients.

Topics: Aged; Body Weight; Fasting; Female; Humans; Hypertension, Renal; Insulin Resistance; Kidney Failure, Chronic; Leptin; Linear Models; Male; Metabolic Syndrome; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Renal Dialysis; Risk Factors

Previous studies from this laboratory have reported a marked attenuation of the renal responses to pharmacologic doses of synthetic murine leptin infused in the spontaneously hypertensive rat (SHR) model compared with normotensive Sprague-Dawley and lean Zucker rat models.. In the present study, the hemodynamic and renal excretory effects of an intravenous bolus administration of pharmacologic doses of synthetic murine leptin were examined in groups of anesthetized SHR with unilateral nephrectomy and renal denervation or sham-denervation of the remaining kidney.. In the SHR with acute renal denervation (N = 8), an intravenous bolus of 1600 microg/kg of leptin produced a significant twofold to fourfold elevation in sodium excretion but did not increase natriuresis in the sham-denervated group (N = 6). Chronic renal denervation of one-week duration (N = 8) was associated with qualitatively and quantitatively similar increases of sodium excretion in response to leptin administration. Mean arterial pressure remained unchanged in all groups after the administration of leptin.. Collectively, these results are interpreted to suggest that the blunted natriuretic and diuretic responses to leptin observed in the SHR with intact renal nerves may be partially explained by the antinatriuretic effect of an enhanced baseline efferent renal sympathetic activity and/or leptin's stimulation of the sympathetic nervous system.

Topics: Animals; Blood Pressure; Body Weight; Denervation; Hypertension, Renal; Kidney; Leptin; Natriuresis; Rats; Rats, Inbred SHR; Sodium; Sympathetic Nervous System; Urine