Cardiovascular effects of melanocortins.

Melanocortins (MSH's) are three structurally related peptides derived from proopiomelanocortin. They regulate several physiologic functions including energy metabolism, appetite, and inflammation. Recent work in rodents has also identified important effects of MSH's, particularly γ-MSH, on sodium metabolism and blood pressure regulation.

Increased renal phosphodiesterase-5 activity mediates the blunted natriuretic response to a nitric oxide donor in the pregnant rat.

Pregnancy is characterized by plasma volume expansion and renal sodium retention with loss of natriuretic response to atrial natriuretic peptide due to increased medullary phosphodiesterase-5 (PDE5). Here, we determined whether natriuretic responses to nitric oxide (NO) are also blunted in pregnancy due to increased PDE5. Anesthetized 16-day pregnant and virgin rats were studied at baseline and during intrarenal infusion of the NO donor spermine NONOate (2.

Tonicity-dependent induction of Sgk1 expression has a potential role in dehydration-induced natriuresis in rodents.

In various mammalian species, including humans, water restriction leads to an acute increase in urinary sodium excretion. This process, known as dehydration natriuresis, helps prevent further accentuation of hypernatremia and the accompanying rise in extracellular tonicity. Serum- and glucocorticoid-inducible kinase (Sgk1), which is expressed in the renal medulla, is regulated by extracellular tonicity.

Evidence for a noradrenergic mechanism causing hypertension and abnormal glucose metabolism in rats with relative deficiency of gamma-melanocyte-stimulating hormone.

A close association between salt-sensitive hypertension and insulin resistance has been recognized for more than two decades, although the mechanism(s) underlying this relationship have not been elucidated. Recent data in mice with genetic disruption of the gamma-melanocyte-stimulating hormone (gamma-MSH) system suggest that this system plays a role in the pathophysiological relationship between hypertension and altered glucose metabolism during ingestion of a high-sodium diet (8% NaCl, HSD). We tested the hypothesis that these two consequences of interrupted gamma-MSH signalling were the result of sympathetic activation by studying rats treated with the dopaminergic agonist bromocriptine (5 mg kg(-1) i.

Abnormal glucose metabolism in hypertensive mice with genetically interrupted gamma-melanocyte stimulating hormone signaling fed a high-sodium diet.

Background: Rodents with deficiency of or resistance to the proopiomelanocortin-derived peptide gamma-melanocyte stimulating hormone (gamma-MSH) develop marked salt-sensitive hypertension. We asked whether this hypertension was accompanied by abnormal glucose metabolism.

Methods: gamma-MSH-deficient Pc2(-/-) mice, and resistant Mc3r(-/-) mice were studied acutely for measurement of blood pressure and glucose and insulin concentrations after > or =1 week of a high-sodium diet (HSD; 8% NaCl) compared to a normal-sodium diet (NSD; 0.

Prevention of salt-induced hypertension by an analog of gamma-melanocyte-stimulating hormone in the rat.

Background: Rats with suppression of pituitary intermediate lobe (IL) function by treatment with the dopaminergic agonist bromocriptine develop salt-sensitive hypertension accompanied by a deficiency of gamma-melanocyte-stimulating hormone (gamma-MSH).

Methods: To study the time course, and establish the causal role, of gamma-MSH deficiency in the development of salt-sensitive hypertension, we instrumented 12 male Sprague-Dawley rats with radiotelemetry transmitters to record intraaortic mean arterial pressure (MAP). One week later, they were placed on a high-sodium diet (8% NaCl, HSD) and received daily intraperitoneal injections of bromocriptine (5 mg/kg).

Cardiovascular and renal actions of melanocyte-stimulating hormone peptides.

Purpose Of Review: Melanocyte stimulating hormones (MSHs, melanocortins) have important roles in feeding and energy metabolism and in inflammation. Recent observations have uncovered major functions for these peptides, particularly gamma-MSH, in cardiovascular regulation and sodium metabolism.

Recent Findings: Both alpha- and gamma-MSH acutely elevate blood pressure and heart rate through central stimulation of sympathetic nervous outflow.

Central receptors mediating the cardiovascular actions of melanocyte stimulating hormones.

Objective: Alpha and gamma-melanocyte stimulating hormones (MSH) are peptides that possess potent hypertensinogenic actions when injected intravenously or intracerebroventricularly. We sought to define the central receptor(s) mediating these cardiovascular actions.

Methods: We gave bolus injections of synthetic alpha or gamma-MSH intravenously or intracerebroventricularly to anesthetized wild-type (Mc3r+/+, Mc4r+/+) mice and mice with targeted disruption of the gamma-MSH receptor (Mc3r-/-) or the melanocortin 4 receptor (Mc4r-/-).

Modulation by dietary sodium intake of melanocortin 3 receptor mRNA and protein abundance in the rat kidney.

Gamma-melanocyte stimulating hormone (gamma-MSH) is a circulating natriuretic peptide hormone derived from proopiomelanocortin (POMC); its concentration in plasma and pituitary POMC mRNA abundance, increase in rats ingesting a high-sodium diet (HSD, 8% NaCl) compared with a low-sodium diet (LSD, 0.07% NaCl). RT-PCR of rat kidney RNA demonstrated reaction products of the expected size in both cortex and medulla for MC3-R, MC4-R, and MC5-R mRNA; no signal for MC1-R or MC2-R was detected.

1,25 dihydroxyvitamin d amplifies type a natriuretic peptide receptor expression and activity in target cells.

1,25 dihydroxyvitamin D (VD) has been shown to exert a number of beneficial effects on cardiovascular function, including reduction in BP and inhibition of cardiac hypertrophy. In an effort to identify a possible mechanistic link between VD and these salutary effects, the role of VD in controlling the activity and expression of the type A natriuretic peptide receptor (NPR-A), a receptor that signals reductions in BP and suppression of cellular growth in the myocardium and vascular wall, was investigated. VD, as well as the nonhypercalcemic analogue RO-25-6760, increased NPR-A-dependent cyclic guanosine monophosphate production and NPR-A gene expression in cultured rat aortic smooth muscle cells.

Appetite and inflammation, nutrition, anemia, and clinical outcome in hemodialysis patients.

Background: Malnutrition-inflammation complex syndrome, an outcome predictor in maintenance hemodialysis (MHD) patients, may be related to anorexia.

Objectives: We examined whether subjectively reported appetite is associated with adverse conditions and increased morbidity and mortality in MHD patients.

Design: A cohort of 331 MHD outpatients was asked to rate their recent appetite status on a scale from 1 to 4 (very good, good, fair, and poor appetite, respectively).

Increased activity of cGMP-specific phosphodiesterase (PDE5) contributes to resistance to atrial natriuretic peptide natriuresis in the pregnant rat.

Increased cGMP-specific phosphodiesterase (PDE5) activity in renal inner medullary collecting duct (IMCD) cells contributes to resistance to atrial natriuretic peptide (ANP) and the excessive sodium retention seen in experimental nephrotic syndrome and liver cirrhosis. Normal pregnancy is also accompanied by sodium retention and plasma volume expansion, and pregnant rats are resistant to the natriuretic action of ANP. The authors investigated a possible role of increased renal PDE5 activity in the physiologic sodium retention of normal rat pregnancy.

Comparing outcome predictability of markers of malnutrition-inflammation complex syndrome in haemodialysis patients.

Background: Markers of malnutrition-inflammation complex syndrome (MICS) are reported to predict mortality and hospitalization in maintenance haemodialysis (MHD) patients. However, it is not clear which one is a more sensitive and stronger predictor of outcome.

Methods: We examined the utility of 10 markers of MICS as predictors of prospective mortality and hospitalization, which included malnutrition-inflammation score (MIS), a fully quantitative score adopted from subjective global assessment, and serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), albumin, pre-albumin, total iron binding capacity, creatinine, total cholesterol and normalized protein nitrogen appearance.

Gamma-MSH, sodium metabolism, and salt-sensitive hypertension.

Alpha-, beta-, and gamma-melanocyte stimulating hormones (MSHs) are melanotropin peptides that are derived from the ACTH/beta-endorphin prohormone proopiomelanocortin (POMC). They have been highly conserved through evolutionary development, although their functions in mammals have remained obscure. The identification in the last decade of a family of five membrane-spanning melanocortin receptors (MC-Rs), for which the melanotropins are the natural ligands, has permitted the characterization of a number of important actions of these peptides, although the physiological function(s) of gamma-MSH have remained elusive.

A low, rather than a high, total plasma homocysteine is an indicator of poor outcome in hemodialysis patients.

An increased level of total plasma homocysteine (tHcy) is a risk factor for poor cardiovascular outcome in the general population. However, a decreased, rather than an increased, tHcy concentration may predict poor outcome in maintenance hemodialysis (MHD) patients, a phenomenon referred to as reverse epidemiology. Associations were examined between tHcy level and markers of malnutrition-inflammation complex syndrome and 12-mo prospective hospitalization and mortality in 367 MHD patients, aged 54.

Association between serum ferritin and measures of inflammation, nutrition and iron in haemodialysis patients.

Background: Serum ferritin is a frequently used marker of iron status in dialysis patients. Iron administration is to be withheld for ferritin values >800 ng/ml according to K/DOQI guidelines. We hypothesized that such non-iron-related factors as elements of the malnutrition-inflammation complex syndrome (MICS) may increase serum ferritin concentration independently of iron status.

Suppression of gamma-melanocyte-stimulating hormone secretion is accompanied by salt-sensitive hypertension in the rat.

Gamma-melanocyte-stimulating hormone (gamma-MSH) is a natriuretic peptide derived from proopiomelanocortin (POMC) in the pituitary neurointermediate lobe (NIL); its plasma concentration in rats doubles after ingestion of a high (HSD; 8% NaCl) compared with a low sodium diet (LSD; 0.07%). Because NIL function is regulated through dopaminergic pathways, we asked whether dopaminergic stimulation with bromocriptine (5 mg/kg IP daily for 1 week) or inhibition with haloperidol (5 mg/kg IP for 1 week) alters the gamma-MSH response to a HSD.

Genetic disruption of gamma-melanocyte-stimulating hormone signaling leads to salt-sensitive hypertension in the mouse.

The gamma-melanocyte-stimulating hormone (gamma-MSH) is a natriuretic peptide derived from the N-terminal region of proopiomelanocortin (POMC). Evidence suggests that it may be part of the coordinated response to a low-sodium diet (LSD). We tested the effect of the HSD (8% NaCl) compared with LSD (0.

Reverse epidemiology of cardiovascular risk factors in maintenance dialysis patients.

Conventional risk factors of cardiovascular disease and mortality in the general population such as body mass, serum cholesterol, and blood pressure are also found to relate to outcome in maintenance dialysis patients, but often in an opposite direction. Obesity, hypercholesterolemia, and hypertension appear to be protective features that are associated with a greater survival among dialysis patients. A similar protective role has been described for high serum creatinine and possibly homocysteine levels in end-stage renal disease (ESRD) patients.

Association among SF36 quality of life measures and nutrition, hospitalization, and mortality in hemodialysis.

Patients on maintenance hemodialysis (MHD) often show substantial reductions in quality of life (QoL). The SF36 (Short Form with 36 questions), a well-documented, self-administered QoL scoring system that includes eight independent scales and two main dimensions, has been widely used and validated. In 65 adult outpatients on MHD, the SF36 and its scales and dimensions, scored as a number between 0 and 100, and the nutritional and inflammatory state measured by subjective global assessment, near-infrared (NIR) body fat, body mass index (BMI), and pertinent laboratory values, including hemoglobin, albumin, and C-reactive protein were assessed.