Plasma Atrial Natriuretic Polypeptide Research Articles

Protective effects of hydroxysafflor yellow A on acute and chronic congestive cardiac failure mediated by reducing ET-1, NOS and oxidative stress in rats RETRACTED ARTICLE

The present study was conducted to investigate whether hydroxysafflor yellow A (HSYA) has a protective effect on acute and chronic heart failure (AHF/CHF) induced by ligation of the left anterior descending coronary artery for 3 h and 8 weeks, respectively. The rats were divided into the following groups: sham operation, coronary artery ligation (CAL), CAL+HSYA (100 mg kg(-1) by gavage) and CAL+diltiazem (20 mg kg(-1) by gavage). In the AHF model, heart function, as determined by haemodynamic studies and echocardiography, was improved significantly by pretreatment with HSYA or diltiazem. Significant reductions in elevated serum creatine phosphokinase, lactate dehydrogenase, malondialdehyde (MDA), glutamic oxalacetic transaminase, glutamic pyruvic transaminase and blood viscosity were observed, and the activity of serum superoxide dismutase (SOD) was enhanced (all P<0.01). In the CHF model, HSYA and diltiazem restored abnormal heart function, and completely suppressed the elevated plasma atrial natriuretic polypeptide (ANP) and endothelin-1 (ET-1), serum and left-ventricular tissue inducible nitric oxide (NO) synthase (iNOS), NO and MDA, and improved the decrease in SOD. HSYA and diltiazem improved cardiac performance in AHF and reduced cardiac remodelling in CHF by reducing tissue weight indices: left ventricular weight/body weight (BW), right ventricular weight/BW, kidney weight/BW and lung weight/BW, and attenuating increases in infarct size, inner diameter of the left ventricle and collagen volume fraction in non-infarcted areas, and the decrease in mean wall thickness of infarcted myocardium. These results suggest that HSYA exerted beneficial actions in cardiac performance in models of both AHF and CHF, mainly by suppressing ET-1, iNOS and oxidative stress in infarcted tissue.

The contribution of an arteriovenous access for hemodialysis to left ventricular hypertrophy

Background: The long-term isolated contribution of hemodialysis arteriovenous access (AVA) to cardiac hemodynamics has not been previously investigated in a prospective manner. Methods: Twelve predialysis patients were studied before and 1 and 3 months after creation of a primary AVA. Evaluation included relevant clinical parameters, echocardiographic studies, and hemodynamic hormones. Results: After creation of an AVA, there was no change in patient weight, blood pressure or hemoglobin level. Cardiac index increased and systemic vascular resistance decreased. Left ventricular mass (LVM) corrected to height increased from 63.8 ± 5.5 to 68.9 ± 4.9 g/m2.7 at 1 month (P = 0.05) and 72.5 ± 8.9 g/m2.7 at 3 months (P < 0.05). This increase in LVM was accounted for mostly by an increase in interventricular septal thickness, whereas left ventricular end-diastolic diameter and posterior wall thickness did not change. The incidence of left ventricular hypertrophy (LVH) increased from 67% at baseline to 83% and 90% at 1 and 3 months, respectively. Left atrial area increased from 17.6 ± 1.0 cm2 at baseline to 19.7 ± 1.3 cm2 at 1 month (P < 0.01) and 20.2 ± 1.2 cm2 at 3 months (P < 0.05). Early diastolic transmitral flow increased from 68.0 ± 4.2 cm/s at baseline to 85.6 ± 7.3 and 89.2 ± 6.5 cm/s at 1 and 3 months, respectively (P < 0.01). Inferior vena cava diameter increased at 1 month and did not change at 3 months. Plasma atrial natriuretic polypeptide levels increased from 268 ± 35 pg/mL (87 ± 11 pmol/L) at baseline to 461 ± 63 pg/mL (150 ± 20 pmol/L) at 1 month (P < 0.01) and 610 ± 96 pg/mL (198 ± 31 pmol/L) at 3 months (P < 0.01). Plasma renin activity and serum aldosterone levels decreased. Plasma angiotensin II, angiotensin-converting enzyme, and endothelin levels did not change. Conclusion: Creation of a hemodialysis AVA is independently associated with further progression of already existing LVH. © 2002 by the National Kidney Foundation, Inc.

Effects of Cilostazol on Heart Rate and its Variation in Patients With Atrial Fibrillation Associated With Bradycardia

Heart-rate (HR) variability is an important predictor of mortality in patients with heart disease. We examined the effects of cilostazol, a quinolinone derivative, on HR and HR variability in patients with chronic atrial fibrillation associated with bradycardia episodes. Thirteen patients with chronic atrial fibrillation associated with bradycardia episodes (minimal HR <40/min and/or pauses, ie, episodes with an RR interval > 2.5 sec) received cilostazol (100 or 200 mg/day) orally for at least 2 months and 24-hour Holter electrocardiography was performed before and after the start of cilostazol administration. Minimal HR was significantly increased, by an average of 14 beats/min (bpm), at 3.3 +/- 0.8 weeks (mean +/- SD) after the start of cilostazol treatment. The number of pauses was significantly decreased. As a consequence, mean HR was increased by an average of 18 bpm. Maximal HR was also increased by an average of 19 bpm. The circadian variation of the HR, determined by cosine fitting, was not changed by cilostazol treatment. The time-domain HR variabilities, ie, the SD of the mean RR interval and the SD of the 5-minute mean RR intervals, were also unchanged. New York Heart Association functional class was significantly improved and the plasma atrial natriuretic polypeptide level was significantly decreased after the initiation of cilostazol treatment. Cilostazol improves the slow HR episodes associated with chronic atrial fibrillation and maintains the HR circadian variation and time-domain variability, indicating that cilostazol has therapeutic utility for the treatment of the slow HR associated with chronic atrial fibrillation.

Glucocorticoids potentiate the action of atrial natriuretic polypeptide in adrenalectomized rats.

Adrenal insufficiency in human and rat is associated with an impairment of the diuretic response to water load, and only glucorticoids (GCs) restore this deficit. Our observation that GCs potentiate atrial natriuretic polypeptide (ANP)-stimulated cGMP production in cultured renal cells prompted us to examine the possibility that GCs may restore the diuretic response through the potentiation of ANP action. Initially, changes in urine volume and ANP levels were studied in adrenalectomized (Adx) and sham-operated intact rats after an oral water load of 5 ml/100 g BW. Urine volume after water load was 4.5 +/- 0.5 ml/30 min in the intact rats, whereas it was 0.8 +/- 0.2 ml/30 min in the Adx rats. In the intact rats, a significant increase in plasma ANP level was observed 30 min after the water load, whereas no increase was observed in Adx rats. This defective ANP response may be involved in the impairment of the diuretic response in Adx rats. Indeed, pretreatment of Adx rats with dexamethasone (Dex, 20 micrograms/100 g BW) increased plasma ANP levels even before water load and improved diuretic response. Subsequently, effect of iv administration of human or rat ANP at a pharmacological dose (2.5 micrograms/100 g BW) on urine volume, osmolarity, and urinary excretion of cGMP, and sodium was studied in Adx rats that received an oral water load 30 min before ANP. Dex treatment was achieved by per os administration 3 h before the ANP injection. In Adx rats, the urine volume after ANP administration was 1.2 +/- 0.1 ml/30 min, and pretreatment with Dex markedly increased the urine volume to 6.3 +/- 0.4 ml/30 min. Dex also increased ANP-induced osmolar and sodium excretion by 2.6- and 2.9-fold, respectively. Although urinary excretion of cGMP was increased in Adx rats by ANP administration, a further significant increase was observed by the pretreatment with Dex. Injection of (Bu)2cGMP to Adx rats pretreated with Dex resulted in a significant increase in urine volume and osmolar and sodium excretion. However, no significant increase in urine volume was observed in Adx rats not pretreated with Dex. The present study suggests that GCs restore the diuretic response to acute water load not only by increasing the secretion of ANP but also by potentiating ANP-stimulated cGMP production. Furthermore, GCs may augment ANP action at one or more steps other than cGMP formation because administration of (Bu)2cGMP to Adx rats did not correct the diuretic response to water load.

Observations on plasma ANP levels during short-term transient myocardial ischemia produced by PTCA in patients with LAD stenosis.

Ten patients with coronary artery disease and stable angina (mean age fifty-seven) were included in the study. Five of the patients had normal left ventricular function, 5 had local hypokinesia or akinesia; 8 had one-stem and 2 had two-stem disease, but all had left anterior descending (LAD) lesions ranging from 75% to 100%. Ejection fraction varied between 35% and 75% (mean 59%). Immunoreactive atrial natriuretic polypeptide (ANP) levels in the femoral vein (FV) and the coronary sinus (CS) were measured before, immediately after, and up to twenty-four hours after percutaneous transluminal coronary angioplasty (PTCA) of the LAD. ANP secretion increased by 83% (FV) and 11% (CS) within minutes after PTCA and reached control levels after thirty to sixty minutes. In patients with hypokinesia of the anterior wall, ANP secretion was significantly lower, 48% (FV) and 11% (CS) respectively. ANP secretion during PTCA was higher in patients with concomitant increase in pulmonary capillary pressure (PCP) but was also observed without an increase of PCP, suggesting ventricular ANP secretion. IN conclusion, transient myocardial ischemia leads to immediate ANP secretion even in the absence of significant pressure elevation in the left atrium. As a part of the continuous medical education program of the American College of Angiology the second part of the paper reviews the mechanisms that allow the ischemic heart to counteract the ischemic condition and thus to escape from myocardial infarction. A review of this subject is presently not available in the literature.

Clinical evaluation of plasma atrial natriuretic polypeptide in patients with respiratory failure in pulmonary tuberculosis

We previously reported the clinical role of plasma immunoreactive atrial natriuretic polypeptide (ANP) and cyclic GMP in patients with respiratory diseases, bronchial asthma (BA), chronic pulmonary emphysema (CPE) and pulmonary insufficiency induced by pulmonary tuberculosis (TBC). In this study, moreover, we divided patients with respiratory failure induced by tuberculosis sequelae into two groups, patients with oxygen therapy group [O2 (+) group] or ordinary practical treatment group [O2 (-) group], and we evaluated the difference of the roles of ANP in two groups and the correlation of ANP and c-GMP with clinical findings, blood gas analysis, electrocardiogram, chest roentogen photography and spirogram in two groups. In conclusion, the respiratory failure in patients with tuberculosis sequelae is compensated by increased cardiac output, and that causes the rising of right atrial pressure. These results show, addition to the basic effects of ANP, the concentration of plasma ANP is released with relating the degree of respiratory failure.

気管支ぜん息患者における血しょう心房性ナトリウム利尿ペプチドの臨床的役割

We previously reported that the atrial natriuretic polypeptide (ANP) caused a relaxant effect with the tissue cyclic GMP (c-GMP) levels on a guinea pig tracheal smooth muscle.We studied plasma immunoreactive ANP and c-GMP concentrations in various situations in patients with respiratory diseases which were divided into 3 groups, patients with bronchial asthma (BA, n=16), patients with chronic pulmonary emphysema (CPE, n=10) and patients with pulmonary insufficiency induced by pulmonary tuberculosis (Tbc, n=44). One hundred and thirteen healthy subjects were also studied as a control group. This is the first report that these clinical markers have been measured at same time in the field of respiratory diseases.In conclusion, 1) Plasma ANP was significantly higher in patients with BA (attack) (P<0.05) and Tbc (P<0.01) than in control. 2) Plasma c-GMP was significantly higher in patients with Tbc (P<0.01) than with BA (remission). 3) There was a significant correlation between plasma c-GMP and log ANP in patients with chronic respiratory disease (r=0.714, P<0.05, n=72). 4) Plasma ANP was significantly higher at attack than at remission (P<0.05).These results indicate that effects of ANP in patients with respiratory disease may be, at least in part, mediated by c-GMP being in the place of cyclic AMP, and ANP induced by pulmonary hypertention may cause a relaxant effect on tracheal and vascular smooth muscle. Therefore, exogenous ANP may also be useful on the therapy of patients with bronchial asthma. such as intractable asthma.

Different mechanisms of polyuria and natriuresis associated with paroxysmal supraventricular tachycardia

The mechanism of polyuria associated with paroxysmal supraventricular tachycardia (SVT) was investigated in 8 patients. SVT was induced artificially and sustained for 60 minutes. Urine and blood samples were collected every 30 minutes. During the latter half of SVT, urine flow increased twofold in the control subjects before SVT. Urinary sodium excretion increased significantly (p < 0.01) within 30 minutes after SVT. Urinary excretion of antidiuretic hormone (ADH) decreased (p < 0.01) during the latter half of SVT and increased (p < 0.01) after SVT, respectively. Plasma level of ADH did not change during SVT but increased (p < 0.05) after SVT. The concentration of plasma atrial natriuretic polypeptide (ANP) increased significantly (p < 0.05) before SVT ended. Urinary excretion of prostaglandin E 2 increased significantly (p < 0.05) after termination of SVT. The percent changes in the urinary excretion of prostaglandin E 2 were correlated (r = 0.713, p < 0.001) with those of ADH. There was also a correlation (r = 0.6, p < 0.001) between the percent changes in the urinary excretion of prostaglandin E 2 and those of sodium. Their findings suggest that the polyuria during SVT is attributed mainly to the inhibition of ADH release and that the natriuresis after SVT is due not only to the increased ANP but also to the increased renal prostaglandin E 2 probably stimulated by ADH.

Pathophysiological Role of Augmented Atrial Natriuretic Polypeptide Gene Expression in DOCA-Salt Hypertension

To elucidate the pathophysiological significance of endogenous atrial natriuretic polypeptide (ANP) in hypertension, we investigated the biosynthesis and secretion of ANP in deoxycorticosterone acetate (DOCA)-salt hypertensive rats and also examined the effect of passive immunization with monoclonal antibody raised against alpha-rat ANP on the development of hypertension in DOCA-salt rats. The plasma ANP level in DOCA-salt rats was significantly elevated in comparison to control rats. While the atrial ANP concentration in DOCA-salt rats was not significantly altered, the atrial level of ANPmRNA in DOCA-salt rats was two-fold higher than that in control rats. These results suggest the augmented biosynthesis of ANP in the atrium and the oversecretion of ANP from the heart in DOCA-salt rats. The levels of ANP and ANPmRNA in the ventricle of DOCA-salt rats exhibited significant increases, compared with those in control rats, suggesting the induction of ANP gene expression in the ventricle of DOCA-salt hypertensive rats under pre/after overload. Weekly intravenous administrations of monoclonal antibody with high affinity for alpha-rat ANP significantly augmented the rise in blood pressure of DOCA-salt rats. These results support the hypothesis that the augmented secretion of ANP is one of the defensive mechanisms to counteract high arterial pressure in this model of hypertension.

Does atrial appendectomy aggravate secretory function of atrial natriuretic polypeptide?

The present study was designed to clarify how atrial appendectomy affects hemodynamics and secretory function of atrial natriuretic polypeptide in the failing heart. Eleven mongrel dogs were prepared for the experimental model of high-output heart failure by creation of arteriovenous fistulas between femoral arteries and veins. Two months after the first operation, effects of bilateral atrial appendectomies on basal and pacing-induced secretions of atrial natriuretic polypeptide were investigated in five dogs with simultaneous measurement of various hemodynamic indices. In the remaining six dogs, used as a control group, pacing-induced secretion of atrial natriuretic polypeptide was examined in the same way as in the appendectomy group. After excision of the atrial appendages, neither systolic blood pressure nor either atrial pressure changed, but plasma atrial natriuretic polypeptide level was decreased (292 +/- 54 to 188 +/- 47 pg/ml, p less than 0.01) and cardiac output fell (3.7 +/- 0.9 to 3.0 +/- 0.8 L/min, p less than 0.01). During pacing-induced tachycardia, the peak level of plasma atrial natriuretic polypeptide was lower in the appendectomy group than in the control groups (593 +/- 213 versus 1170 +/- 324 pg/ml, p less than 0.05), despite similar left atrial pressures in the two groups. The excised appendages contained approximately 30% of the total amount of atrial natriuretic polypeptide. These results demonstrate that atrial appendectomy decreases secretory function of atrial natriuretic polypeptide and reduces cardiac output in dogs with experimental high-output heart failure.

The Medical Evaluation of Patients with Diabetes Mellitus in Exercise Therapy

To investigate myocardial ischemia during exercise, submaximal exercise testing with electrocardiogram and thallium 201-myocardial scintigraphy was performed in non-insulin-dependent diabetics. The relationship between plasma atrial natriuretic polypeptide (ANP) levels in response to exercise and cardiac function assessed by echocardiography was also examined. The following results were obtained: 1) Twelve of the 66 diabetics (18.2%) had ischemic ST-segment changes in exercise ECGs, compared with 4 of 75 control subjects (5.3%)(p less than 0.05). Of the 12 diabetics with positive exercise ECGs, 10 were asymptomatic. 2) The washout rate in thallium-201 myocardial scintigraphy was significantly less in diabetics with positive exercise ECGs (36.5 +/- 4.1%) than in controls (51.9 +/- 2.8%)(p less than 0.05). 3) Although no difference in heart rate were observed between diabetics and controls, diabetic patients had significantly higher systolic blood pressure than controls during all stages of exercise and at maximal exertion. Rate pressure products in stages 1 and 2 were significantly higher in diabetics than in controls. 4) The increase of plasma ANP concentration during moderate exercise (VO2 max 60%) was significantly greater in diabetics than in controls (32.3 +/- 11.9 pg/ml vs. 15.0 +/- 1.7 pg/ml)(p less than 0.02). 5) There was a significant correlation between the increase in plasma ANP during exercise and the levels of left ventricular diastolic function (A/R:r = 0.504, p less than 0.05, IRT:r = 0.587, p less than 0.02), assessed by echocardiography, in diabetics. In conclusion, this study demonstrated that the frequency of asymptomatic myocardial ischemia during exercise was higher in diabetics than in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Efferent mechanisms mediating renal sodium and water excretion induced by centrally administered serotonin

Treatments that increase central extracellular serotonin (5-HT) also increase Na excretion. Efferent renal sympathetic nerve activity (ERSNA) contributes to the control of Na and water reabsorption. To determine whether renal nerves play a role in the 5-HT-induced natriuresis, we examined the effect of intracerebroventricular (icv) injection of vehicle or 5-HT (20 micrograms) on Na, K, and urine excretion rates, as well as mean arterial pressure and heart rate in unanesthetized, hydrated rats with renal nerves intact or sectioned. Renal denervation attenuated the natriuresis produced by 5-HT but not the antidiuresis observed 15-30 min after injection. Central 5-HT produced brief pressor and bradycardic responses, followed by continued bradycardia and hypotension, which were more pronounced in intact rats. In other experiments, circulating levels of arginine vasopressin (AVP) and plasma atrial natriuretic polypeptide (ANP) were measured 15 min after icv injection of 5-HT. 5-HT significantly increased circulating AVP, but plasma ANP remained unchanged. These results suggest that renal nerves participate in the natriuresis elicited by centrally administered 5-HT through a decrease in ERSNA. The antidiuresis observed after central 5-HT may be due to an increase in AVP release.

Dynamic exercise-induced elevation in plasma levels of atrial natriuretic peptide in patients with effort angina pectoris

We investigated the relationship between plasma atrial natriuretic polypeptide (ANP) levels and hemodynamic indices during dynamic exercise testing in 15 patients with effort angina pectoris. Patients exercised on an angina-limited, supine, multistage bicycle ergometer, and plasma ANP levels and hemodynamic indices were measured at rest, at peak exercise, and 6 minutes after exercise. Plasma ANP levels increased significantly at peak exercise. Pulmonary artery wedge pressure (PAWP) and coronary sinus blood flow (CSBF) were significantly correlated with plasma ANP levels before and at peak exercise (PAWP: r = 0.69, p < 0.001; CSBF; r = 0.45, p < 0.05). In six of eight patients whose PAWP exceeded 20 mm Hg at peak exercise, plasma ANP levels were increased at 6 minutes after exercise, whereas PAWP had decreased relative to the values obtained at peak exercise. Plasma ANP concentrations at 6 minutes after exercise were not correlated with PAWP at the same time. However, PAWP at peak exercise was correlated with the plasma ANP levels at 6 minutes after exercise ( r = 0.80, p < 0.001). These results suggest that in patients with effort angina pectoris left ventricular dysfunction resulting from exercise-induced myocardial ischemia may increase preload excessively and may contribute to the excess secretion of ANP after dynamic exercise.

Atrial natriuretic polypeptide is removed by the lungs and released into the left atrium as well as the right atrium in humans

To examine the sites of release and removal of plasma atrial natriuretic polypeptide plasma levels in the femoral vein, right atrium, pulmonary artery, pulmonary capillary bed, left atrium and aortic root were measured in 11 control subjects and 22 patients with mitral stenosis. Mean plasma natriuretic polypeptide levels in the femoral vein, right atrium, pulmonary artery, pulmonary capillary bed, left atrium and aortic root were, respectively, 64 ± 29, 124 ± 72,103 ± 44, 83 ± 30,106 ± 46 and 101 ± 35 pg/ml in the control subjects and 321 ± 170, 500 ± 234, 458 ± 266, 356 ± 209,434 ± 222 and 432 ± 217 pg/ml in the patients with mitral stenosis.In both the control subjects and the patients with mitral stenosis, there was a significant increase between the femoral vein and the right atrium and between the pulmonary capillary bed and the left atrium and a significant decrease between the pulmonary artery and the pulmonary capillary bed. Blood samples were also taken simultaneously from the pulmonary vein and the pulmonary capillary bed, as well as from the pulmonary artery and the left atrium, in 25 patients (11 control subjects, 5 patients with mitral stenosis and 9 patients with atria[ septa[ defect). There was no difference in plasma atria[ natriuretic polypeptide levels between the pulmonary capillary bed and the pulmonary vein in these 25 patients.It is concluded that atrial natriuretic polypeptide 1) is released into the left as well as the right atrium, and 2) is removed by the lungs.

Atrial natriuretic polypeptide after burn injury: blood levels and physiological role in rats

To define the relationship between atrial natriuretic polypeptide and the physiological changes of water and electrolytes after burns, the changes in plasma hormonal levels, including atrial natriuretic polypeptide, and urinary water and sodium excretions were examined in burned rats. Further, to elucidate the physiological significance of atrial natriuretic polypeptide after burns, the effects of a specific antiserum against atrial natriuretic polypeptide were determined in burned rats. Plasma atrial natriuretic polypeptide levels in rats following 30 per cent BSA full skin thickness burns were elevated for sustained periods (432.3 ± 156.5 pg /ml, P<0.01 on day 1 postburn, 244.5±73.7 pg/ml, P<0.05 on day 3 postburn). Urine volume and sodium excretion decreased significantly during the first 72 h after burns. On day 3 postburn, urine volume and sodium excretion began to increase significantly. Specific rabbit antiserum against atrial natriuretic polypeptide was injected into the burned rats during this diuretic phase. Significant inhibition of diuresis and natriuresis was observed after the injection of antiserum (27.5 ± 2.4 per cent decrease in urine volume, 57.1 ± 10.4 per cent decrease in sodium excretion). These results suggest that atrial natriuretic polypeptide plays a physiological role in the regulation of urinary water and sodium excretion after burns.

Release of ANP and its physiological role in pulmonary injury due to HCl

The effect of pulmonary injury induced by aspiration of HCl on plasma atrial natriuretic polypeptide (ANP) level was examined in rats given a constant infusion of water and electrolytes. In addition, using specific antiserum against ANP, we investigated the physiological role of ANP in rats after HCl aspiration. Rats were housed individually in metabolic cages and were given a constant infusion of sodium solution via catheters chronically inserted into the jugular vein. Plasma ANP levels were elevated at 3 and 24 h after tracheal injection of 0.2 ml of 0.1 N HCl via the cricothyroid membrane. Urine volume and urinary sodium excretion increased during the first 24 h after acid aspiration. However, this increase was reduced by the injection of anti-ANP serum. Furthermore, the injection of anti-ANP serum resulted in a significant (P less than 0.05) increase in wet lung weight from a value of 0.74 +/- 0.06 (HCl aspiration with normal rabbit serum injection) to 0.83 +/- 0.07% of body weight. These results indicate that ANP plays a physiological role in the regulation of urinary water and sodium excretion after pulmonary acid injury and suggest that ANP elevated in plasma after pulmonary injury may prevent pulmonary edema with its diuretic action and/or some direct action on water movement in the lung.

Phasic plasma atrial natriuretic polypeptide changes in DOCA-salt hypertensive rats.

We determined plasma and cardiac immunoreactive atrial natriuretic polypeptide (ir-ANP) levels in rats treated with deoxycorticosterone acetate (DOCA) and sodium chloride for 1, 7, and 28 days. Systolic blood pressure of DOCA-salt rats began to increase from the 7th day and reached 191 +/- 7 mmHg at the 28th day. One day after treatment with DOCA-salt, plasma levels of ir-ANP were increased compared to that of control rats. This was accompanied by decreased cardiac ir-ANP content. However, at the 7th day of DOCA-salt treatment, both plasma and cardiac ir-ANP levels of DOCA-salt rats were not different from those of control animals. At the 28th day, DOCA-salt rats had high plasma ir-ANP levels and no significantly different cardiac ir-ANP content compared to the controls. These data suggest that there are time-related changes in plasma ANP concentration during the development of DOCA-salt hypertension and higher plasma ANP levels might not necessarily be associated with a decreased cardiac ANP content.

Effect of vagotomy on brain and plasma atrial natriuretic peptide during hemorrhage

These experiments investigated the change in brain, atrial, and plasma concentrations of atrial natriuretic polypeptide (ANP) after a 33% hemorrhage and the role of vagal nerve input in these changes. In rats, hemorrhage decreased plasma ANP from 246 +/- 48 to 41 +/- 7 pg/ml, but in a hypothalamic tissue block ANP increased from 19.0 +/- 0.9 to 25.5 +/- 0.6 ng/g tissue (P less than 0.05). Bilateral vagotomy was followed by a very large increase in plasma ANP to 703 +/- 198 pg/ml. Atrial pressures, however, fell after vagotomy from 2 +/- 2 to 1 +/- 1 mmHg. Therefore, the effect was not due to increased atrial stretch. Right atrial ANP levels were also elevated by vagotomy, but left atrial ANP concentrations did not change with vagotomy or hemorrhage. After hemorrhage in vagotomized rats, plasma ANP decreased to 79 +/- 6 pg/ml. After vagotomy, the ANP concentration in the hypothalamic block did not rise in response to hemorrhage. The results indicate that the vagus nerves provide a tonic inhibition of ANP levels in atria and plasma. The results cannot be explained by atrial distension. The results show independence of brain and plasma ANP and uncover a tonic vagal inhibition of ANP release.

Increased Synthesis and Secretion of Atrial Natriuretic Polypeptide During Viral Myocarditis

To elucidate the pathophysiological role of atrial natriuretic polypeptide (ANP) in diseased hearts, ANP levels in atrial and ventricular tissues and plasma were investigated in mice with congestive heart failure after viral myocarditis. The study was performed on day 14 after encephalomyocarditis viral inoculation, when congestive heart failure developed. The atrial ANP level increased to a value two times higher than that of noninoculated age-matched mice (the control mice). The ventricles of the control mice contained an approximately 1,000-fold lower ANP level than the atrial ANP level. The ventricular ANP concentration of the infected mice showed about a 21 times higher level than the control value. The plasma ANP level was also elevated 20 times. On immunofluorescence studies, increase of immunostaining were found in the atria of the infected mice, and positive staining appeared on the cardiocytes in almost all areas of the remaining ventricular tissues of the infected mice, whereas staining was not found on the ventricles of the control mice. The staining seemed particularly strong in the area surrounding the myocardial lesions. These results indicate that atrial and ventricular ANP synthesis and ANP secretion increase in the heart with viral myocarditis. The marked increase in the ventricular ANP level suggests that the ventricle is another important production site for circulating ANP.

Plasma atrial natriuretic polypeptide as an index of left ventricular end-diastolic pressure in patients with chronic left-sided heart failure

To evaluate the relationship between plasma atrial natriuretic polypeptide (ANP), hemodynamic parameters, and plasma catecholamines and, in addition, to determine whether circulating ANP is metabolized in the pulmonary circulation, plasma concentrations of ANP were determined in 40 patients with chronic left-sided heart failure. After at least 30 minutes of bed rest with the patient in the supine position, blood samples were drawn simultaneously from both the main pulmonary artery (mPA) and the ascending aorta (Ao) before administration of contrast medium. The plasma ANP concentrations significantly decreased from the mPA to the Ao (135.3 ± 18.1 pg/ml vs 127.4 ± 19.4 pg/ml; mean ± SEM, p < 0.05). The plasma ANP level in the mPA correlated with the plasma norepinephrine level in the Ao ( r = 0.71, p < 0.01), right atrial pressure ( r = 0.34, p < 0.05), mean pulmonary capillary wedge pressure ( r = 0.829, p < 0.001), and left ventricular end-diastolic pressure (LVEDP) ( r = 0.88, p < 0.001). Of the various hemodynamic parameters and plasma catecholamine concentrations in the Ao, only LVEDP was found to be an independent and significant predictor of plasma ANP levels in the mPA. These results indicate that ANP released from the heart is regulated mainly by preload (LVEDP) in cases of left-sided heart failure and that circulating ANP is metabolized in the pulmonary circulation. In conclusion, the plasma ANP concentration may be a useful noninvasive index of LVEDP in patients with chronic left-sided heart failure.