Plasma human atrial natriuretic peptide levels in patients with liver cirrhosis

Plasma levels of human atrial natriuretic peptide (hANP) were investigated in patients with liver cirrhosis, and the relationships between plasma hANP levels and the following factors were studied: presence of ascites, serum and urine electrolytes, plasma renin activity, angiotensin I and II, aldosterone, catecholamines, prostaglandin derivatives, conventional liver function tests and circulating blood volume. Plasma hANP level was significantly (P less than 0.05) elevated in patients with ascites (mean = 58.6 pg/mL, s.e.m. = 8.8) compared with cases without ascites (mean = 36.6 pg/mL, s.e.m. = 2.6). With the disappearance of ascites, the level fell to normal in most cases. Urine sodium excretion was positively correlated with plasma hANP in patients without ascites, but not in patients with ascites. The plasma hANP level was disproportionately high for the rate of urinary Na excretion in cirrhotics with ascites. The plasma hANP level was not correlated with any of the other factors such as blood volume, renin-angiotensin-aldosterone levels, catecholamines and liver function tests. These results suggest that plasma hANP levels are elevated in cirrhotic patients especially with ascites, but the natriuretic response of the kidney to this raised hANP level can be impaired in patients with liver cirrhosis and ascites.     

Plasma levels of brain natriuretic peptide,cyclic 3'5'-guanosine monophosphate,endothelin 1, and noradrenaline in patients with chronic congestive heart failure

Chronic congestive heart failure (CHF) is a complex clinical syndrome characterized by marked neurohormonal activation which may lead to further decompensation of the circulatory system. This study was undertaken to establish the role of certain hormones in pathogenesis of congestive heart failure. Plasma levels of brain natriuretic peptide (BNP), cyclic 3'5'-guanosine monophosphate (c-GMP), endothelin 1 (ET-1), and noradrenaline (NA) were examined in patients in patients with CHF and with decompensation of circulatory system. The survey was made in 92 patients with CHF, among them there were 42 females aged 50-76 years (mean 66 years) and 50 males aged 53-76 years (mean 68 years). All patients were divided into 3 groups according to NYHA classification. On admission blood samples were taken from all patients to determine plasma levels of BNP, c-GMP, ET-1, and NA. Then patients received captopril and furosemide. Next blood samples were taken between 5 and 7 day of the treatment, after entire remission symptoms of decompensation. Plasma levels of BNP, c-GMP, ET-1, and NA were estimated with radioimmunoassay. Our study showed that plasma levels of ET-1, BNP, c-GMP, and NA were increased in patients with CHF. 5-7 days of the treatment with ACE inhibitor and diuretic caused significant decrease of ET-1, BNP, and c-GMP levels, but did not influence NA plasma levels. Determination of ET-1, BNP, c-GMP, and NA plasma levels may be a noninvasive method useful in estimation of degree of CHF and efficacy of the treatment.     

The effect of altering haemodynamics on the plasma concentrations of natriuretic peptides in heart failure

BACKGROUND: Natriuretic peptide levels reflect haemodynamics in patients with heart failure and may serve as biochemical markers of cardiac filling pressures. The purpose of this study was to detect differences in the kinetic profile between atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and their N-terminal fragments N-ANP and N-BNP, in response to rapid and persistent vasodilatation. METHODS: Sixteen men and four women aged 63.0+/-10.4 (mean+/-S.D.) with symptomatic congestive heart failure (NYHA III) and pulmonary capillary wedge pressure (PCWP)>18 mm Hg, received a 24-h infusion of nitroglycerin (N=8) or nicorandil (N=12). A reduction of PCWP was achieved for the duration of the study. Natriuretic peptides were measured by radioimmunoassay at baseline, 1, 3, 6, 12 and 24 h. RESULTS: PCWP and right atrial pressure fell rapidly and then increased modestly. ANP and N-ANP demonstrated a similar pattern. In contrast, BNP and N-BNP levels fell steadily throughout the observation period. This was accompanied by a continuous reduction of systemic vascular resistance (SVR). PCWP was highly correlated to the levels of all the natriuretic peptides. Using a longitudinal regression model evaluating responses over time, we found separate, significant relationships between all peptides and haemodynamic variables CONCLUSION: The atrial natriuretic peptides reflect rapid changes in filling pressures while the B-type peptides respond much slower. B-type peptides are less sensitive to short-term changes in filling pressures, but should reflect changes in SVR better during vasodilator therapy.     

Modulation of human neutrophil chemotactic responses by cyclic 3',5'-guanosine monophosphate and cyclic 3',5'-adenosine monophosphate.

Cyclic 3',5'-guanosine monophosphate (cGMP) and cyclic 3',5'-adenosine monophosphate (cAMP) and compounds known to effect the intracellular concentrations of these nucleotides were examined for their ability to effect human neutrophil (PMN) responsiveness to chemotactic stimulation. Incubation of neutrophils with agents recognized to promote increases in intracellular cAMP in a variety of tissues (i.e., epinephrine, norepinephrine, isoproterenol, histamine, cholera toxin, and prostaglandin E-1 and E-2) or with cAMP inhibited the leukotactic response to a bacterial chemotactic factor. In contrast, cGMP and compounds which have been shown to promote increases in intracellular cGMP concentration (i.e., acetylcholine, carbamylcholine, phorbol myristate acetate, and prostaglindin F-2-alpha) markedly enhanced the neutrophil chemotactic response. The inhibitory or stimulatory influences on chemotactic responsiveness promoted by several of the agents could be shown to be blocked by a specific pharmacologic antagonist of the particular compound tested. These data support the hypothesis that cGMP and cAMP can provide opposing regulatory influences on certain cellular functions; in this case, directed motility of leukocytes.     

Haemodynamic responses to a ring‐deleted analogue of atrial natriuretic peptide in rats with cirrhosis

Abstract: Aims: In cirrhosis, the effects of selective activation of atrial natriuretic peptide (ANP) R2‐receptors on haemodynamics, endogenous ANP (ANP1–28) and sodium excretion are unknown. The aim of the present study was to examine the effects of selective activation of ANP‐R2 receptors by ANP4–23 (a ring‐deleted analogue of endogenous ANP) on haemodynamics, plasma ANP1–28 concentrations and urinary sodium excretion in conscious cirrhotic and normal rats. Methods: Haemodynamics and sodium excretion were measured prior to and following administration of ANP4–23. Plasma ANP1–28 concentrations were also measured. Results: In cirrhotic rats, ANP4–23 significantly decreased portal pressure and tributary blood flow by 15% and 25% respectively but significantly increased portal territory vascular resistance by 30%. Systemic and renal haemodynamics were not altered by ANP4–23. In normal rats, ANP4–23 did not significantly change splanchnic, renal and systemic haemodynamics. In both groups of rats, ANP4–23 increased plasma ANP1–28 concentrations but did not change sodium excretion. Conclusions: ANP4–23 administration induced splanchnic vasoconstriction in cirrhotic but not in normal rats. ANP4–23‐elicited vasoconstriction caused a portal hypotensive effect in cirrhotic rats. Finally, in both groups, ANP4–23 caused an increase in plasma ANP1–28 concentrations but did not increase sodium excretion.     

Plasma levels of atrial natriuretic peptide in patients with liver cirrhosis and its relation to ascites and renal function

Plasma immunoreactive a-human atrial natriuretic polypeptide (Ir-α-hANP) was measured by radioimmunoassay in 21 cirrhotics and 10 normal subjects. Average of Ir-α-hANP level in cirrhotics was significantly higher than in normal subjects (125.8 ± 79.6 versus 28.7 ± 12.2 pg/ml, P< 0.001). In cirrhotics without ascites, Ir-α-hANP levels were positively correlated with creatinine clearance (Ccr) and urinary sodium excretion, suggesting that α-hANP was closely related to renal circulation and sodium homeostasis. One the contrary, in cirrhotics with ascites Ir-α-hANP levels were negatively correlated with Ccr. Urinary sodium excretion in cirrhotics with ascites and Ccr more than 50 ml/min was positively correlated with Ir-α-hANP levels. However, cirrhotics with ascites and Ccr less than 50 ml/min excreted little sodium in spite of high Ir-α-hANP levels. On the basis of the Ir-α-hANP before and after treatment of ascites, cirrhotics with ascites were subdivided into 2 groups. In group I Ir-α-hANP decreased from high values and in group II it was further elevated from slightly high values by treatment. The difference in renal function and plasma volume may account for the difference in Ir-α-hANP changes in the 2 groups. This study was presented in part in the 22nd meeting of the Japanese Association for the Study of the Liver, June 6,1986, Tokyo, Japan and in 22nd meeting of the European Association for the Study of the Liver, September 5, 1987, Torino, Italy.     

Urinary excretion of cyclic 3',5'-adenosine monophosphate and cyclic 3',5'-guanosine monophosphate during and after pregnancy.

Urinary cyclic AMP and cyclic GMP excretions were measured in 24-h urine specimens obtained from 89 women at various times during their normal uncomplicated intrauterine pregnancies and from 49 women at various times after the births of their normal healthy infants. Cyclic AMP excretion increased steadily from the beginning of the second trimester or earlier until late in the third trimester, reaching a peak excretion approximately 40% greater than that of normal nonpregnant women. The cyclic AMP excretion dropped abruptly by the first day after parturition to levels which were not significant different from those of normal non-pregnant women. In contrast, cyclic GMP excretion increased rapidly during the first trimester and remained relatively constant during the remainder of the pregnancy, reaching a peak excretion of about 140% greater than that of normal nonpregnant women. Furthermore, it decreased slowly toward normal levels, but was still significantly elevated six weeks after parturition. The factors responsible for the increased excretion of cyclic AMP during pregnancy and for the increased cyclic GMP during and after pregnancy are not known.     

Relationships between the severity of cirrhosis and haemodynamic values in patients with cirrhosis

Abstract The relationship between the severity of cirrhosis and systemic and hepatic haemodynamic values was evaluated in 193 patients with cirrhosis, most of whom were diagnosed with post-necrotic cirrhosis. It was found that the hepatic venous pressure gradient and cardiac output in Pugh's A patients (13.6 ± 4.8 mmHg and 6.2 ± 1.6 L/min, mean ± s.d.) were significantly lower than in both Pugh's B (16.8 ± 4.3 mmHg and 7.3 ± 2.1 L/min) and Pugh's C (18.8 ± 5.5 mmHg and 7.4 ± 2.3 L/min) patients ( P < 0.01), respectively. In contrast, the systemic vascular resistance in Pugh's A patients (1232 ± 369 dyn/s per cm⁵) was significantly higher than in both Pugh's B (1016 ± 345 dyn/s per cm⁵) and Pugh's C (935 ± 234 dyn/s per cm⁵) patients ( P < 0.01), respectively. Additionally, not only was there a positive correlation found between Pugh's score and cardiac output and hepatic venous pressure gradient, but a negative correlation was found between Pugh's score and systemic vascular resistance. It was also confirmed that the degree of portal hypertension and the hyperdynamic circulation were more severe in patients with ascites than in those without ascites. However, there were no statistically significant differences in hepatic venous pressure gradient among patients with F1, F2 and F3 esophageal varices (15.7 ± 4.0, 17.0 ± 4.8 and 18.0 ± 4.8 mmHg, respectively). It is concluded that in those patients with cirrhosis, the severity of cirrhosis is closely related to the degree of the hyperkinetic circulatory state and portal hypertension.     

Plasma brain natriuretic peptide and atrial natriuretic peptide concentrations correlate with left ventricular end-diastolic pressure

The present study was designed to investigate whether brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) plasma concentrations correlate with left ventricular end-diastolic pressure (LVEDP), pulmonary capillary wedge pressure (PCWP), diastolic pulmonary arterial pressure (DPAP), right atrial pressure (RAP), or ejection fraction (EF). Plasma BNP and ANP levels were determined by commercial radioimmunoassays (Peninsula) after Sep Pak C₁₈ extraction in blood samples withdrawn from the pulmonary artery and the left ventricle or from the left ventricle and the femoral vein in 85 patients undergoing diagnostic cardiac catheterization. Linear and nonlinear regression analysis and the paired sample f-test were applied to the data. Pulmonary arterial plasma BNP and ANP levels showed a close nonlinear correlation with LVEDP (BNP: r=0.94, p < 0.001; ANP: r=0.81, p < 0.001), a significant linear correlation with PCWP, DPAP, and RAP, and a significant negative correlation with EE ANP concentrations decreased significantly from the pulmonary artery to the left ventricle and from the left ventricle to the femoral vein (p < 0.001). BNP levels also decreased significantly between the left ventricle and the femoral vein (p < 0.001), but there was no significant difference between pulmonary arterial and left ventricular BNP concentrations. BNP and ANP concentrations correlated significantly between pulmonary arterial and left ventricular blood samples (BNP: r = 0.99, ANP: r = 0.93, p < 0.001) and between left ventricular and peripheral blood samples (BNP: r=0.99, ANP: r=0.94, p<0.001). The present data suggest that peripheral plasma BNP and ANP levels are useful noninvasive indices of cardiac performance.     

Plasma interleukin-8 levels in patients with post-hepatitic cirrhosis: Relationship to severity of liver disease, portal hypertension and hyperdynamic circulation

The present study investigated plasma levels of interleukin-8 (IL-8) in patients with post-hepatitic cirrhosis and correlated it with the severity of liver diseases and haemodynamic parameters. Plasma IL-8 levels were significantly higher in 57 post-hepatitic cirrhotic patients (7.5 ± 1.8 pg/mL; P< 0.005) than those in 41 healthy subjects (2.0 ± 0.2 pg/mL). Elevated (> 5 pg/mL) plasma IL-8 levels were found in up to 30% of cirrhotic patients. In cirrhotic patients, plasma IL-8 levels progressively increased in relation to the severity of liver dysfunction (4.5 ± 1.0, 4.9 ± 1.4 and 20.5 ± 8.3 pg/mL for Pugh's class A, B and C, respectively; P<0.005). A significant correlation was observed between plasma IL-8 levels and serum bilirubin levels (r = 0.72; P<0.001). There were no differences in the hepatic venous pressure gradient (15.4 ± 1.1 vs 15.1 ± 0.9 mmHg; P>0.05) and systemic vascular resistance (1119 ± 118 vs 1199 ± 54 dyn.s/cm⁵; P>0.05) between cirrhotic patients with and without elevated plasma IL-8 levels. In addition, plasma IL-8 levels did not correlate with hepatic venous pressure gradient (r = 0.26; P>0.05) and systemic vascular resistance (r=-0.24; P>0.05). These results demonstrate that plasma IL-8 levels are increased in patients with post-hepatitic cirrhosis. The severity of liver cirrhosis is an important factor for the occurrence of enhanced IL-8 levels. IL-8 does not play a role in the hyperdynamic circulation observed in patients with post-hepatitic cirrhosis.     

Circulating and hepatic endocannabinoids and endocannabinoid‐related molecules in patients with cirrhosis

Background/Aims: Endocannabinoids include anandamide (AEA) and 2‐arachidonoylglycerol (2‐AG). Endocannabinoid‐related molecules like oleoyl‐ethanolamine (OEA) and palmitoyl‐ethanolamine (PEA) have also been identified. AEA contributes to the pathogenesis of cardiovascular alterations in experimental cirrhosis, but data on the endocannabinoid system in human cirrhosis are lacking. Thus, we aimed to assess whether circulating and hepatic endocannabinoids are upregulated in cirrhotic patients and whether their levels correlate with systemic haemodynamics and liver function. Methods: The endocannabinoid levels were measured in peripheral and hepatic veins and liver tissue by isotope‐dilution liquid chromatography‐atmospheric pressure chemical ionization‐mass spectrometry. Systemic haemodynamics were assessed by the transthoracic electrical bioimpedance technique. Portal pressure was evaluated by hepatic venous pressure gradient. Results: Circulating AEA and, to a greater extent, PEA and OEA were significantly higher in cirrhotic patients than in controls. PEA and OEA were also increased in the cirrhotic liver tissue. AEA, OEA and PEA levels were significantly higher in peripheral than in the hepatic veins of cirrhotic patients, while the opposite occurred for 2‐AG. Finally, circulating AEA, OEA and PEA correlated with parameters of liver function, such as serum bilirubin and international normalized ratio. No correlations were found with systemic haemodynamics. Conclusions: The endocannabinoid system is upregulated in human cirrhosis. Peripheral AEA is increased in patients with a high model of end‐stage liver disease score and may reflect the extent of liver dysfunction. In contrast, the 2‐AG levels, the other major endocannabinoid, are not affected by cirrhosis. The upregulation of the endocannabinoid‐related molecules, OEA and PEA, is even greater than that of AEA, prompting pharmacological studies on these compounds.     

Effect of terlipressin on blood volume distribution in patients with cirrhosis

Background: Patients with cirrhosis and portal hypertension have an altered blood volume distribution and a hyperdynamic systemic circulation. Terlipressin is known to reduce portal pressure by decreasing splanchnic inflow, but its effect on the blood volume distribution is unknown. The aim of the study was to investigate changes in regional blood volume distribution and systemic haemodynamics after administration of terlipressin to patients with cirrhosis. Methods: Blood volume distribution was determined in 13 patients with cirrhosis and portal hypertension by a dual‐head gamma‐camera technique and systemic haemodynamics was measured before and after intravenous administration of terlipressin (2?mg). Results: Terlipressin increased the blood volume in the thorax region (+6.0%, P?P?P?r?=?0.88, P?Conclusions: Terlipressin ameliorates the hyperdynamic circulation, increases thorax and liver blood volumes, but produces no effect on the splanchnic blood volume. Besides decreasing the splanchnic inflow, terlipressin may affect portal pressure by causing vasodilatation of intrahepatic vessels.     

Pressure-dependent,enhanced natriuretic response to low-dose,atrial natriuretic peptide infusion in essential hypertension

Abstract. Objective. To examine whether the effect of atrial natriuretic peptide (ANP) on renal glomerular and tubular segmental handling of sodium in patients with essential hypertension is pressure dependent. Design. Part 1. The renal effects of a low-dose continuous infusion (10 ng kg^?1 min^?1) with ANP for 1 h were compared in 10 untreated essential hypertensives (EH) and 13 normotensive control subjects (CS). Part 2. The hypertensives were studied on another day with ANP infusion during preceding acute BP reduction with sodium nitroprusside infusion (NP). The results were compared with those obtained during infusion with ANP + placebo (Part 1). Methods. Lithium clearance was used to estimate the proximal tubular reabsorption of sodium. Results. Part 1. Atrial natriuretic peptide caused an exaggerated increase in urinary sodium excretion (+ 102 vs. + 38%; P < 0.05), fractional excretion of sodium (+ 80 vs. + 37%; P < 0.05), and urinary output (+ 56 vs. + 8.3%; P < 0.05) in EH compared with CS. Glomerular filtration rate and filtration fraction increased to the same degree in both groups. Absolute lithium clearance (C_L1) increased and FE_L1 tended to increase (P = 0.061) in EH, but these were unchanged in CS. The increase in plasma cyclic guanosine 5′-phosphate (cGMP) and urinary excretion of cGMP and the decrease in plasma aldosterone during ANP infusion were the same in the two groups. Part 2. During NP infusion the natriuresis caused by ANP in EH was reduced (+ 51 vs. +99%; P <0.05). The relative changes in GFR, C_L1, and FE_L1 during ANP infusion were not affected by the preceding BP reduction with NP. Mean arterial pressure was reduced from 122 to 101 mmHg during NP infusion. The relative increase in sodium excretion in EH was significantly correlated to mean arterial pressure. Conclusions. Low-dose ANP infusion causes an exaggerated natriuresis in untreated essential hypertensives due to a more pronounced reduction in tubular reabsorption. After BP reduction, the natriuresis induced by ANP in essential hypertensives is decreased, probably due to a less pronounced reduction in tubular reabsorption beyond the proximal tubules. We suggest that the enhanced natriuretic response to ANP in EH is secondary in some degree to the elevated systemic pressure.     

Elevated nitric oxide and 3′,5′ cyclic guanosine monophosphate levels in patients with alcoholic cirrhosis

AIM： To evaluate whether serum levels of nitric oxide （NO^.） and plasma levels of cyclic guanosine monophosphate （cGMP） and total glutathione （GSH） are altered in patients with alcoholic cirrhosis and to examine their correlation with the severity of liver disease.
METHODS： Twenty-six patients with alcoholic liver cirrhosis were studied. Serum levels of NO^. and plasma levels of cGMP and GSH were measured in 7 patients with compensated alcoholic cirrhosis （Child-Pugh A） and 19 patients with advanced cirrhosis （Child-Pugh B and C）. The model for end-stage liver disease （MELD） score was evaluated. Sixteen healthy volunteers served as controls. Liver enzymes and creatinine levels were also tested.
RESULTS： NO^. and cGMP levels were higher in patients with Child-Pugh B and C cirrhosis than in Child-Pugh A cirrhosis or controls （NO^.： 21.70 ± 8.07 vs 11.70 ± 2.74; 21.70± 8.07 vs 7.26 ± 2.47 μmol/L, respectively; P 〈 0.001） and （cGMP： 20.12 ± 6.62 vs 10.14 ± 2.78; 20.12 ± 6.62 vs 4.95 ± 1.21 pmol/L, respectively; P 〈 0.001）. Total glutathione levels were lower in patients with Child-Pugh B and C cirrhosis than in patients with Child-Pugh A cirrhosis or controls （16.04 ± 6.06 vs 23.01 ± 4.38 or 16.04 ± 6.06 vs 66.57 ±26.23 μmol/L, respectively; P 〈 0.001）. There was a significant correlation between NO^. and cGMP levels in all patients with alcoholic cirrhosis. A significant negative correlation between reduced glutathione/glutathione disulfide and the MELD score was found in all cirrhotic patients.
CONCLUSION： Our results suggest a role for oxidative stress in alcoholic liver cirrhosis, which is more significant in decompensated patients with higher levels of NO^. and cGMP and lower GSH levels than in compensated and control patients. Altered mediator levels in decompensated patients may influence the hemodynamic changes in and progression of liver disease.     

Plasma concentrations of atrial natriuretic peptide during physical exercise in patients with congestive heart failure

Summary Plasma concentrations of atrial natriuretic peptide (ANP) were measured in 25 patients with organic heart disease during physical exercise (baseline and maximum workload) in order to investigate if the responsiveness of stimulated release of ANP is still preserved in patients with heart failure and chronically elevated cardiac filling pressures. Since plasma concentrations of ANP are known to be positively correlated with mean right atrial pressures (RAP), the patients were divided into two groups according to their resting RAP: group I: those with normal RAP ( 5 mmHg; n=11); group II: those with elevated RAP (>5 mmHg; n=14). Under baseline conditions RAP (3.2±0.4 mmHg vs. 8.8±0.7 mmHg; p<0.01), pulmonary artery diastolic pressure (PADP; 9.5±0.9 mmHg vs. 17.9±1.8 pg/ml; p.<0.01), and plasma ANP levels (128±19 pg/ml vs. 204±60 pg/ml; p<0.06) were significantly lower in group I than in group II. Both at rest and during maximum workload, plasma ANP concentrations were closely related to RAP, PADP, and mean pulmonary artery pressures in both groups.During exercise in all patients, RAP and PADP significantly increased, as well as plasma ANP concentrations. Similar increments in plasma ANP concentrations were accompanied by greater changes in RAP in group II than in group I. However, identical changes in PADP lead to identical increments in plasma ANP concentrations in both groups.In conclusion, the increments of plasma ANP concentrations during physical exercise were independent of the resting values of PADP, RAP, and plasma ANP concentrations. During exercise the increments in plasma ANP concentrations for identical changes of PADP were not significantly influenced by the resting conditions; only in patients with elevated RAP at rest did increments in RAP during exercise induce a slightly reduced ANP release compared with patients who had normal right ventricular filling pressures. These data indicate that the responsiveness of ANP release during physical exercise is only slightly impaired in patients with heart failure and chronically elevated cardiac filling pressures.Dedicated to Professor Dr. F. Loogen on the occasion of his 70th birthday.     

Relationship between plasma levels of atrial natriuretic peptide and cyclic guanosine monophosphate in patients with heart diseases

The relation of plasma levels of atrial natriuretic peptide (ANP) to those of cyclic 3', 5'-guanosine monophosphate (cGMP) was studied in 43 patients with various heart diseases. Plasma levels of both ANP and cGMP were significantly (p less than 0.001) elevated in 34 patients with chronic heart diseases, and a significant positive correlation was observed between the two variables (r = 0.706, p less than 0.01). Clinical improvement of congestive heart failure resulted in a concomitant decrease in plasma ANP and cGMP levels in 6 patients. In 3 patients with paroxysmal atrial fibrillation, plasma levels of ANP and cGMP increased markedly during arrhythmia. These results indicate that increased circulating ANP may stimulate cGMP production in target cells, which in turn raises plasma levels of cGMP in humans.     

Low plasma concentrations of atrial natriuretic peptide in untreated hypothyroid patients

A group of patients with primary hypothyroidism has been studied, and it is reported that low serum levels of thyroid hormones are accompanied by low plasma atrial natriuretic peptide (ANP) concentrations. While the correlation between ANP and thyroid hormone levels is strong, no correlation was found between ANP and heart rate or arterial blood pressure. It is suggested that thyroid hormones directly stimulate the release of ANP from atrial cardiocytes.     

Effect of anaemia on haemodynamics in patients with cirrhosis

BACKGROUND: It has been suggested that increased blood haemoglobin attenuates splanchnic vasodilatation in portal-hypertensive rats by nitric oxide inactivation. However, the haemodynamic effect of anaemia in cirrhotic patients of varying severity has been rarely discussed. The aim of this study was to evaluate the influence of anaemia on systemic and splanchnic haemodynamics in cirrhotic patients of differing severity. METHODS: Two hundred and twenty-five cirrhotic patients were included in this study. All biochemical and haemodynamic results were utilized for analysis. Anaemia was defined as a haemoglobin level below the cut-off value of 12 g/dL, which might best predict low systemic vascular resistance. RESULTS: Compared with non-anaemic patients, anaemic patients had decreased mean arterial pressure (90 +/- 1 vs 95 +/- 1 mmHg, P = 0.002), and decreased systemic vascular resistance (1022 +/- 25 vs 1227 +/- 30, P < 0.0001), and increased cardiac index (4.3 +/- 0.1 vs 3.8 +/- 0.1 L/min per m2, P < 0.0001) and increased hepatic venous pressure gradient (16.7 +/- 0.5 vs 14.4 +/- 0.6 mmHg, P = 0.006). Haemoglobin concentration exerted an influence on the degree of vasodilatation in cirrhotic patients, with Child-Pugh's A class (but not in Child-Pugh's B and C classes), and in patients without ascites (but not in patients with ascites). CONCLUSIONS: It was concluded that anaemia has a negative effect on hyperdynamic circulation in patients with early cirrhosis which is not observed in patients with advanced cirrhosis.