AIMTo investigate the effect of vasonatrin peptide (VNP) on the expression of C-type natriuretic peptide receptor (NPR-C) in hypoxic rat hearts.

METHODSRats were divided randomly into three groups: control group, hypoxia group(3-28 d) and VNP (25-75 microg/kg per day) + hypoxia group. The plasma concentration of atrial natriuretic peptide (ANP) in rats was measured by the means of radioimmunoassay. Furthermore, quantitative PCR was used to examine the NPR-C mRNA level in rat hearts.

RESULTSThe plasma concentration ANP in rats was significantly higher than that of control group, and VNP (75 microg/kg per day) made it more higher. Hypoxia for 3 day of had no significant effect on the NPR-C mRNA level in rat hearts, while hypoxia for 7-28 d significantly increased the level of NPR-C mRNA in a time dependent manner. VNP (50-75 microg/kg per day) significantly reduced the NPR-C mRNA level in rat hearts in a dose dependent manner.

CONCLUSIONVNP increases the plasma concentration of ANP in hypoxic rats. Hypoxia can increase expression of NPR-C in rat hearts significantly, which can be inhibited by VNP.

Animals ; Atrial Natriuretic Factor ; blood ; pharmacology ; Hypoxia ; metabolism ; Male ; Natriuretic Peptide, C-Type ; metabolism ; Natriuretic Peptides ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Atrial Natriuretic Factor ; metabolism

OBJECTIVEAtrial natriuretic peptide (ANP) is a cardiac hormone with many biological effects. Hypersecretion may lead to hyponatremia. This study examined the umbilical ANP levels in high risk neonates.

METHODSA total of 117 high risk neonates born between June, 2004 and June, 2005 were divided into Simple asphyxia and Normal score groups according to their Apgar's scores. The Simple asphyxia group was subdivided into Mild (n=20) and Severe asphyxia groups (n=17), and the Normal score group was subdivided into Infection (n=25) and Non-infection groups (n=55). Forty normal neonates were used as the Control group. The samples of umbilical cord blood were collected at delivery and the umbilical ANP levels were measured by radioimmunoassay. Meanwhile the sodium levels in the peripheral vein were measured.

RESULTSThe mean umbilical ANP levels in high risk neonates were significantly higher than those in the normal neonates. A more significant increase of the umbilical ANP level was observed in premature infants (1.46 +/- 0.39 ng/mL), and neonates with serious infection (1.16 +/- 0.35 ng/mL) and with severe asphyxia (2.12 +/- 0.46 ng/mL) compared with the normal neonates (0.62 +/- 0.33 ng/mL; P < 0.01). The serum sodium level was negatively correlated with the umbilical ANP level (r=-0.99, P < 0.01).

CONCLUSIONSThe umbilical ANP levels increased significantly in the high risk neonates, suggesting high risk neonates are susceptible to hyponatremia.

Atrial Natriuretic Factor ; blood ; Fetal Blood ; chemistry ; Humans ; Hyponatremia ; etiology ; Infant, Newborn ; Risk ; Sodium ; blood

It is not clear whether Ca2+-induced Ca2+ release from the sarcoplasmic reticulum (SR) is involved in the regulation of atrial natriuretic peptide (ANP) release. Previously, we have shown that nifedipine increased ANP release, indicating that Ca2+ entry via voltage-gated L-type Ca2+ channel activation decreases ANP release. The purpose of the present study was two-fold: to define the role of SR Ca2+ release in the regulation of ANP release and whether Ca2+ entry via L-type Ca2+ channel is prerequisite for the SR-related effect on ANP release. Experiments were performed in perfused beating rabbit atria. Ryanodine, an inhibitor of SR Ca2+ release, increased atrial myocytic ANP release (8.69+/-3.05, 19.55+/-1.09, 27.31+/-3.51, and 18.91+/-4.76% for 1, 2, 3, and 6microM ryanodine, respectively; all P< 1) with concomitant decrease in atrial stroke volume and pulse pressure in a dose-dependent manner. In the presence of thapsigargin, an inhibitor of SR Ca2+ pump, ryanodine-induced increase in ANP release was not observed. Thapsigargin attenuated ryanodine-induced decrease in atrial dynamic changes. Blockade of L-type Ca2+ channel with nifedipine abolished ryanodine-induced increase in ANP release (0.69+/-5.58% vs. 27.31+/-3.51%; P< 0.001). In the presence of thapsigargin and ryanodine, nifedipine increased ANP release and decreased atrial dynamics. These data suggest that Ca2+-induced Ca2+ release from the SR is inversely involved in the regulation of atrial myocytic ANP release.
Atrial Natriuretic Factor* ; Blood Pressure ; Nifedipine ; Ryanodine ; Sarcoplasmic Reticulum* ; Stroke Volume ; Thapsigargin

To evaluate the relationship between plasma level of immunoreactive atrial natriaretic factor(IR-ANF) and atrial functional index, we studied 28 cardiac patients undergoing cardiac catheterization.Plasma level of IR-ANF in aorta or pulmonary artery was significantly correlated with mean pulmonary capillary wedge pressure, right atrial mean pressure and pulmonary arterial mean pressure, but not with left artrial dimension. To evaluate the relationship between plasma level of IR-ANF and ventricular function index, we selected 13 patients who had normal artrial pressure and no mitral valular disease among 28 patients.Among ventricular functional indices, only left ventricualr end diastolic pressure was significantly correlated with plasma level of IR-ANF in aorta or pulmonary artery. Other indices, such as cardiac index, ejection fraction and aortic systolic blood pressure were not correlated with plasma level of IR-ANF in aorta or pulmonary artery. We concluded that increase in either left atrial pressure may trigger ANF release in man, although ventricles may not be involved in ANF release significantly.
Aorta ; Atrial Natriuretic Factor* ; Atrial Pressure ; Blood Pressure ; Hemodynamics* ; Humans ; Plasma* ; Pulmonary Artery ; Pulmonary Wedge Pressure ; Ventricular Function

BACKGROUNDThe abnormal blood volume regulation is one of the most important pathogenesis in postural tachycardia syndrome in children. This study was designed to investigate the plasma atrial natriuretic peptide and antidiuretic hormone levels in postural tachycardia syndrome children, and their associations with the changes in heart rate and blood pressure in head-up test.

METHODSTwenty-one postural tachycardia syndrome patients ((12 ± 2) years) and 26 healthy children ((12 ± 1) years) were included. According to blood pressure changes in head-up test, the postural tachycardia syndrome patients were divided into two subgroups: postural tachycardia syndrome with orthostatic hypertension and postural tachycardia syndrome without orthostatic hypertension. The plasma atrial natriuretic peptide and antidiuretic hormone levels were measured using enzyme-linked immunosorbent assay.

RESULTSThe plasma atrial natriuretic peptide level in postural tachycardia syndrome patients was higher than the control (P = 0.004), whereas the difference in plasma antidiuretic hormone level between postural tachycardia syndrome and controls was not significant (P = 0.222). The plasma antidiuretic hormone level of patients suffering from postural tachycardia syndrome with orthostatic hypertension was much higher than that of children having postural tachycardia syndrome without orthostatic hypertension (P < 0.05). In postural tachycardia syndrome patients, the upright max heart rate was positively correlated with the plasma atrial natriuretic peptide level (r = 0.490, P < 0.05) and the upright systolic blood pressure was positively correlated with the plasma antidiuretic hormone levels (r = 0.472, P < 0.05).

CONCLUSIONSThere was a disturbance of plasma atrial natriuretic peptide and antidiuretic hormone in postural tachycardia syndrome children.

Adolescent ; Atrial Natriuretic Factor ; blood ; Case-Control Studies ; Child ; Humans ; Hypertension ; blood ; Postural Orthostatic Tachycardia Syndrome ; blood ; Vasopressins ; blood

BACKGROUND: Head-down suspension (HDS) of rats has been used as a model for the simulation of a microgravity environment. Atrial natriuretic peptide (ANP), C-type natriuretic peptides (CNP) and their receptors are found in the kidney, suggesting that these peptides could play a significant physiological role in the kidney. Therefore, this study was investigated the changes in the adaptations of renal natriuretic peptides and their receptors syntheses after 4 weeks of HDS in rats. METHODS: Unanesthetized, unrestrained, male Sprague-Dawley rats were subjected to either a horizontal position (control rats) or a -45degreeshead-down tilt using the tail-traction technique (HDS rats). This study observed the renal syntheses of natriuretic peptides as a expression of ANP and CNP mRNA, and also determined the expression of A-type natriuretic peptide receptor (NPR-A) mRNA and B-type NPR (NPR-B) mRNA. The expressions of natriuretic peptide and NPR mRNA were measured by reverse transcription-polymerase chain reaction with [(32)P]-dCTP following 4 weeks of HDS in the kidney of both control and HDS rats. RESULTS: After 4 weeks of HDS, the expression of ANP mRNA significantly (P<0.01) decreased, while CNP mRNA expression was showed the non-significant increasing trend in the kidney of HDS rats. NPR-A, which binds with ANP, was significantly (P<0.001) decreased in renal mRNA expression of HDS rats compared with controls. Expression in mRNA of NPR-B, which binds with CNP, showed a slightly decreasing trend in the kidney of rats following HDS. CONCLUSION: These results suggest that the renal adaptation following 4 weeks of HDS exerts to maintain the blood volume and electrolyte balance through attenuation of syntheses in the natriuretic peptide and its binding receptor, especially in ANP rather than in CNP systems.
Animals ; Atrial Natriuretic Factor ; Blood Volume ; Humans ; Kidney ; Male ; Natriuretic Peptides* ; Peptides ; Rats* ; Rats, Sprague-Dawley ; Receptors, Peptide ; RNA, Messenger* ; Water-Electrolyte Balance ; Weightlessness

The renal function is under regulatory influence of central nervous system, in which various neurotransmitter and neuromodulator systems take part, and it has been known that kallikrein-kininogen- kinin system exists also in the brain, but its physiological role remains to be explored. This study was, therefore, undertaken to delineate the possible role of central kinin system in the regulation of renal function. Kallikrein given into a lateral ventricle(icv) of rabbit brain in doses ranging from 3 to 30 microgram/kg icv elicited increases in Na excretion and the fraction of filtered sodium excreted(FENa), as well as in urine flow rate. K excretion, however, did not parallel the Na excretion, but tended to decrease when the natriuresis reached its peak. Renal blood flow and glomerular filtration did not significantly change. Neither did free water reabsorption significantly change, but tended to decrease. The systemic blood pressure slightly increased. When 30 microgram/kg kallikrein was given intravenously, all the parameters of renal function and systemic blood pressure did not show any increase but decrease, primarily by decreased renal hemodynamics, resulting from transient hypotension. In experiments in which the plasma ANP was measured, the ANP level markedly increased, reaching more than 5 times the control value 25min after 30 microgram/kg icv, and lasting until the end of the experiment at 80min. The renal nerve activity increased with kallikrein, 30 microgram/kg icv, peaking at 1 min but it remained slightly increased until about 40 min, and then slightly declined. This indicates that the increased renal nerve activity may have antagonized or ameliorated the natriuretic effect of icv kallikrein. Lys-bradykinin(kallidin), a cleavage product from kallidinogen by kallikrein, when given icv in doses of 0.3 to 30 microgram/kg also produced increased Na excretion and diuresis. When CHA, a kallikrein inhibitor, was given icv in doses of 3-30 microgram/kg, elicited antidiuresis and antinatriuresis. However, pretreatment with CHA tended slightly to suppress the kallikrein effect. These results indicate that the central kallikrein- kinin system is involved in the central regulation of renal function, the activation of the system in the CNS resulting in increased natriuresis and diuresis, which are related to increased plasma ANP level, with the possible antagonistic effects of increased renal nerve activity.
Atrial Natriuretic Factor ; Blood Pressure ; Brain ; Central Nervous System ; Diuresis ; Filtration ; Hemodynamics ; Hypotension ; Kallidin* ; Kallikreins* ; Natriuresis ; Natriuretic Agents ; Neurotransmitter Agents ; Plasma ; Renal Circulation ; Sodium ; Water

BACKGROUND: Left ventricular hypertrophy(LVH) is one of the complications of hypertension and has been known as an independent risk factor of cardiovascular complications. Recently, it has been reported that hypertensive patients with LVH had the most advanced extracardiac target-organ damage compared with other groups. Previous reports have shown that mean plasma atrial natriuretic peptide(ANP) and brain natriuretic peptide(BNP) levels in hypertensive patients are higher than in normotensive subjects. Therefore, in this study, we investigated the relationships between the plasma ANP and BNP levels and the degree of LVH in hypertensive patients and in normotensive subjects and also investigated the clinical significance of measurement of plasma ANP and BNP levels. METHODS: In all study subjects, left ventricle mass index(LVMI) and left ventricle geometry were measured by M-mode echocardiography. Measurements were made by the recommendations of the American Society of Echocardiography. Plasma ANP and BNP levels were measured by radioimmunoassay method. RESULTS: 1) 57% of the hypertensive patients had eccentric hypertrophy and 6% had concentric hypertrophy. 2) LV mass and LVMI of normotensive subjects and hypertensive patients were 169+/-53 g, 229+/-64 g and 99+/-27.3 g/m2, 142+/-37.7 g/m2, respectively(P<0.05). 3) There were statistically significant correlations between blood pressure and LVMI in all subjects(r=.43, P<0.05). 4) Plasma ANP levels were significantly increased in hypertensive patients than normotensive subjects (28.2+/-14.3 pg/mL and 42.8+/-26 pg/mL, respectively; P<0.05). 5) Plasma BNP levels were significantly increased in hypertensive patients than normotensive subjects (18.4+/-5.4 pg/mL and 36.5+/-26 pg/mL; respectively, P<0.05). 6) Plasma BNP levels were significantly increased in 63% of the hypertensive patients with LVH(P<0.05). 7) There were statistically significant correlations between blood pressure and plasma ANP and BNP levels(ANP:r=.39, p<0.05, BNP:r=.31, P<0.05). CONCLUSIONS: Plasma ANP and BNP levels were increased in the hypertensive patients but only plasma BNP levels were significantly increased in the hypertensive patients with LVH. Measurement of plasma BNP levels may be useful for early detection of LVH, an independent risk factor of cardiovascular complications. Therefore intensive blood pressure control in these patients may reduce cardiovascular morbidity and mortality.
Atrial Natriuretic Factor ; Blood Pressure ; Brain* ; Echocardiography ; Heart Ventricles ; Humans ; Hypertension* ; Hypertrophy ; Hypertrophy, Left Ventricular ; Mortality ; Natriuretic Peptides* ; Plasma* ; Radioimmunoassay ; Risk Factors

Selective inhibition of phosphodiesterase (PDE) 5 opened a new therapeutic approach for cardiovascular disorders. Therefore, the effect of PDE5 inhibition on the cardiac function should thoroughly be defined. The purpose of the present study was to define the effects of sildenafil, a selective inhibitor of PDE5, on the atrial cGMP efflux, atrial dynamics, and the release of atrial natriuretic peptide (ANP). By perfusing rabbit left atria to allow atrial pacing, changes in atrial stroke volume and pulse pressure, transmural extracellular fluid translocation, cGMP efflux, and ANP secretion were measured. SIN-1, an NO donor and soluble (s) guanylyl cyclase (GC) activator, and C-type natriuretic peptide (CNP), an activator of particulate (p) GC activator, were used. Sildenafil increased basal levels of cGMP efflux slightly but not significantly. Sildenafil in a therapeutic dose increased atrial dynamics (for atrial stroke volume, 2.84+/-1.71%, n=12, vs -0.71+/-0.86%, n=21; p<0.05) and decreased ANP release (-9.02+/-3.36%, n=14, vs 1.35+/-3.25%, n=23; p<0.05), however, it had no effect on the SIN-1- or CNP-induced increase of cGMP levels. Furthermore, sildenafil in a therapeutic dose accentuated SIN-1-induced, but not CNP-induced, decrease of atrial pulse pressure and ANP release. These data indicate that PDE5 inhibition with sildenafil has a minor effect on cGMP levels, but has a distinct effect on pGC-cGMP- and sGC-cGMP-induced contractile and secretory function.
Atrial Natriuretic Factor ; Blood Pressure ; Cyclic Nucleotide Phosphodiesterases, Type 5* ; Extracellular Fluid ; Guanylate Cyclase ; Humans ; Natriuretic Peptide, C-Type ; Stroke Volume ; Tissue Donors ; Sildenafil Citrate

A long-term effect of pentobarbital on the atrial natriuretic peptide (ANP) system was investigated. The experimental group of rats (Sprague-Dawley, male) was one week previously treated with pentobarbital (50 mg/kg, intraperitoneal), and the control was an age-matched group of rats which had never been anesthetized. ANP reaponse to volume-expansion (VE) induced by intravenous infusion of iso-oncotic saline over 30 min (total volume infused amounted up to 5% body weight) was examined under thiopental anesthesia (50 mg/kg, intraperitoneal). Basal plasma ANP level did not significantly differ between the experimental and control groups. Following VE, while the plasma ANP five-fold increased in the control, it rather decreased in the experimental group. Despite the different ANP responses, the magnitude of urinary responses (volume and sodium excretion) to VE did not differ between the two groups. Right and left atrial tissue contents of ANP were significantly lower in the experimental group than in the controL In another series of experiments, the two-kidney, one clip rats were made under either pentobarbital or ether anesthesia and the blood pressure and ANP responses were compared. While the magnitude of blood pressure increases did not differ, the plasma ANP level measured on Day 12 after the clipping was lower in the pentobarbital group than in the ether group. These results suggest that pentobarbital has a long-term inhibitory effect on the ANP system. Its physiological significance in blood pressure and body fluid homeostasis remains to be determined.
Anesthesia ; Animals ; Atrial Natriuretic Factor ; Blood Pressure ; Body Fluids ; Ether ; Homeostasis ; Infusions, Intravenous ; Pentobarbital* ; Plasma ; Rats* ; Sodium ; Thiopental