Left Atrial Levels Research Articles

E0096 The study on the relations between aldosterone and atrial interstitial remodelling and atrial fibrillation

ObjectiveTo investigate the relations between aldosterone (Ald) and atrial interstitial remodelling and atrial fibrillation (AF).Methods18 healthy male hybrid dogs aged 15–18 months were divided into three groups randomly, the control...

Function of cardiac β 1- and β 2-adrenoceptors of newborn piglets: Role of phosphodiesterases PDE3 and PDE4

The structures of porcine and human β 2-adrenoceptors differ but the repercussions for porcine cardiac function are unknown. We investigated the function of porcine β 2-adrenoceptors in 3 cardiac regions, sinoatrial node, left atrium and right ventricle of newborn piglets. Both (−)-noradrenaline and (−)-adrenaline caused sinoatrial tachycardia: 60 ± 10% and 62 ± 7% of the maximum response ( E max) to (−)-noradrenaline (− logEC 50 = 9.0) and (−)-adrenaline (− logEC 50 = 7.5) respectively, were resistant to antagonism by the β 1-selective CGP20712A (2-hydroxy-5-[2-[[2-hydroxy-3-[4-[1-methyl-4-(trifluoromethyl)-1H-imidazol-2-yl]phenoxy]propyl]amino]ethoxy]-benzamide) (300 nM) but antagonized by β 2-selective ICI118551 (erythro(±)-[1-(2,3-dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol) (50 nM), consistent with mediation through β 2-adrenoceptors. The phosphodiesterase3-selective inhibitor cilostamide and phosphodiesterase4-selective inhibitor rolipram did not affect catecholamine chronotropic potencies. Only small CGP20712A-resistant positive inotropic effects of (−)-adrenaline were detected in the left atria (13 ± 2% of E max) and ventricular trabeculae (14 ± 5% of E max). The atrial inotropic responses to (−)-noradrenaline and (−)-adrenaline faded; fades were prevented by rolipram but not cilostamide or concurrent cilostamide + rolipram respectively. (−)-Noradrenaline (ICI118551 present) increased left atrial cAMP levels through β 1-adrenoceptors that were markedly enhanced by rolipram but unaffected by cilostamide. Concurrent cilostamide + rolipram uncovered inotropic and cAMP responses to (−)-adrenaline (CGP20712A present). We conclude that sinoatrial β 2-adrenoceptors are more important than β 1-adrenoceptors in the mediation of tachycardia caused by both (−)-noradrenaline and (−)-adrenaline in the newborn piglet. β 2-adrenoceptors have only a minor role in the mediation of left atrial and ventricular inotropic effects of (−)-adrenaline. Catecholamine-evoked tachycardia is not controlled by PDE3 or PDE4. PDE4, but not PDE3, controls the atrial inotropic and cAMP β 1-adrenoceptor-mediated responses to (−)-noradrenaline. Both PDE3 and PDE4 blunt left atrial inotropic and cAMP responses to (−)-adrenaline through β 2-adrenoceptors.

B-type natriuretic peptide predicts recurrence of atrial fibrillation after pulmonary vein antral isolation

Background: Recurrence of atrial fibrillation (AF) occurs in up to 25% of patients after pulmonary vein antral isolation (PVAI). Recently, B-type natriuretic peptide (BNP) and C-reactive protein (CRP) have been associated with AF. We aimed to test the hypothesis that elevated preablation BNP or CRP levels can predict the recurrence of AF post-PVAI. Methods: BNP and CRP levels were prospectively drawn on all patients before ablation on the day of the scheduled procedure. Follow-up was performed by weekly transtelephonic transmissions, even if asymptomatic, for 3 months and scheduled Holter monitoring at follow-up. Uniand multivariate analyses were performed on demographic, clinical and echo data, CRP and BNP to determine predictors of AF recurrence. For regression analysis log BNP and log CRP were used because these values were skewed. Results: Between 3/03 and 1/04, 521 patients underwent PVAI. After 280 136 days of follow-up 20% of patients (102/521) had recurrence of AF, defined as recurrence after 8 weeks post PVAI. There was no difference in gender distribution (25% vs 30% females), hypertension, LV function (55.8 8% vs 55.6 6%), left ventricular hypertrophy (LVH), left atrial size, history of coronary artery disease (CAD), beta-blocker or pre-procedural antiarrhythmic drug use between the patients who developed recurrence of AF and those who did not. Pre-op plasma BNP and CRP levels were higher in the recurrence group (median 87pg/ml vs 58 pg/ml, Inter Quartile Range, IQR, [44,195] vs [25,114], p 0.005 for BNP and 2.6 mg/l vs 2.1mg/l, IQR [1.15,5.5] vs [1.02,4.4] for CRP). In regression analysis that included age, gender, hypertension, LV function, LVH, left atrial size, CAD, drug use, CRP and BNP levels, only BNP predicted recurrence of AF (Odds Ratio 3.2, 95% CI: 1.7-6.0, p 0.001). Conclusion: Pre-ablation plasma BNP level is an independent predictor of AF recurrence after PVAI. CRP levels were not predictive of recurrence. BNP may be a more sensitive marker of atrial remodeling than CRP, atrial size or LV function. AB8-3

Regional Left Atrial Coagulation and Fibrinolytic Activities in Patients With Mitral Stenosis

Systemic thromboembolism is a major complication of mitral stenosis (MS), especially in those patients having atrial fibrillation (AF). Recent evidence has suggested that regional left atrial coagulation activity may be increased in MS and may contribute to the pathophysiology of left atrial thrombus. However, the relation of left atrial coagulation activity to factors that predispose to left atrial thrombus formation is unknown. Also, the relations between left atrial and systemic coagulation activity, fibrinolysis, and platelet activation remain unresolved. Left atrial and peripheral venous levels of fibrinogen, antithrombin III, factor VII and factor VIII for coagulation, D-dimer, tPA and PAI-I, plasmin and antiplasmin for fibrinolysis, and platelet factor 4 and vWF for platelet activation, and endothelial dysfunction were measured in 46 patients with MS and normal clotting times who were undergoing percutaneous mitral valvuloplasty. Left atrial tPA, plasmin, PAI-I, antiplasmin, PF4, and vWF levels exceeded the corresponding peripheral venous levels (P < 0.05) in patients with MS, being more significant in the AF subgroup. There were no significant differences between left atrial and peripheral venous levels of fibrinogen, D-dimer, factor VII, and factor VIII within the patient group (P > 0.05). The results suggest that there are significant variations in the indices of coagulation, fibrinolytic system and platelet activation, and endothelial dysfunction between left atrial and peripheral venous blood samples of patients with MS that may be due to limited spillover from the left atrium to the systemic circulation.

The endothelin antagonist BQ123 reduces pulmonary vascular resistance after surgical intervention for congenital heart disease

Objective: Postoperative pulmonary hypertension in children after surgical intervention for congenital heart disease has been attributed to failure of the pulmonary endothelium to provide adequate vasodilation. Although we have shown that the impaired vasodilatory component attributable to the l-arginine-nitric oxide pathway is almost completely reversible, a nonrestorable component persists, implying an additional vasoconstrictive mechanism in postoperative pulmonary endothelial dysfunction. In this study of children after surgical intervention for congenital heart disease, we measured endothelin-1 levels and used BQ123, a selective endothelin-A receptor antagonist, together with inhaled nitric oxide to discriminate dysfunctional pulmonary endothelial vasodilation from endothelin-mediated pulmonary vasoconstriction. Methods: All children were examined early after surgical intervention in the intensive care unit. Pulmonary vascular resistance (with respiratory mass spectrometry), as well as arterial and venous endothelin-1 levels (measured by means of a quantitative enzyme-linked immunosorbent assay), were determined in 7 children (age range, 3.3-13.7 months; median age, 6.3 months) with intracardiac shunting defects at baseline and during ventilation with a fraction of inspired oxygen of 0.65, with additional BQ123 (0.1 mg/kg infused over 20 minutes), and with inhaled nitric oxide (20 ppm). Results: Pulmonary vascular resistance decreased from 7.7 ± 3.4 at baseline to 6.1 ± 2.8 Woods units · m−2 (P =.022) at a fraction of inspired oxygen of 0.65 and to 4.7 ± 2.7 Woods units · m−2 (P =.013) during BQ123 infusion. Inhaled nitric oxide had no further effect on pulmonary vascular resistance. Left atrial endothelin-1 levels (1.35-5.12 pg/mL; mean, 2.4 pg/mL) correlated significantly with the decrease in pulmonary vascular resistance in response to BQ123 infusion (r2 = 0.89, P =.003). Conclusion: Postoperative elevation of pulmonary vascular resistance in children after surgical intervention for congenital heart disease is responsive to endothelin-A blockade with BQ123. Increased levels of endothelin-1 predict the response to this therapy, which might become an important addition to the clinical armamentarium in postoperative pulmonary hypertensive disease.J Thorac Cardiovasc Surg 2002;124:435-41

C-reactive protein and paroxysmal atrial fibrillation: evidence of the implication of an inflammatory process in paroxysmal atrial fibrillation

Background — Detection of inflammation is best achieved by measurements of C-reactive protein (CRP).We investigated whether inflammation might promote the development of paroxysmal atrial fibrillation (PAF), and whether high levels of CRP are associated with an increased risk of PAF.Methods — We assessed the levels of CRP and other risk factors in patients with PAF of recent onset (<24 h), compared with age and sex matched controls with the same risk factors who had normal sinus rhythm. Patients with thyrotoxicosis, mitral stenosis, pulmonary emboli or pericarditis were excluded. Fifty patients with PAF and 50 control subjects were finally included. All patients received amiodarone (2.7 g over 24 hours).Results — Conversion to normal sinus rhythm was achieved within 24 h in 40 patients. CRP levels were higher (P<0.001) in the PAF group (median = 0.80, min = 0.00, max = 5.90 mg/dl) compared with controls (median = 0.04, min = 0.00, max = 0.48 mg/dl). In the PAF group CRP levels were higher (P<0.001) for patients who failed to be cardioverted (median = 2.12, min = 0.80, max = 5.90 mg/dl) compared to cardiovertors. Nevertheless, CRP levels in patients who underwent successful cardioversion (median = 0.50, min = 0.00, max = 2.53 mg/dl) were higher compared with controls (P<0.001). Finally, CRP was higher in non-cardiovertors vs. control group, p<0.001. After multivariate adjustment left atrial size (OR, 4.4) and CRP levels (OR, 3.3) were significantly associated with successful cardioversion to sinus rhythm.Conclusion — These results suggest that CRP has a strong association with PAF and support the hypothesis that CRP is a potent determinant of successful cardioversion of PAF in sinus rhythm.

Effects of balloon mitral valvuloplasty on systemic and regional left atrial levels of prothrombin fragment 1+2 in mitral stenosis: authors’ reply

Effects of balloon mitral valvuloplasty on systemic and regional left atrial levels of prothrombin fragment 1+2 in mitral stenosis: authors’ reply

Effects of balloon mitral valvuloplasty on systemic and regional left atrial levels of prothrombin fragment 1+2 in mitral stenosis

Effects of balloon mitral valvuloplasty on systemic and regional left atrial levels of prothrombin fragment 1+2 in mitral stenosis

Effects of balloon mitral valvuloplasty on systemic and regional left atrial levels of prothrombin fragment 1+2 in mitral stenosis

Effects of balloon mitral valvuloplasty on systemic and regional left atrial levels of prothrombin fragment 1+2 in mitral stenosis

Effects of balloon mitral valvuloplasty on systemic and regional left atrial levels of prothrombin fragment 1+2 in mitral stenosis: authors’ reply

Effects of balloon mitral valvuloplasty on systemic and regional left atrial levels of prothrombin fragment 1+2 in mitral stenosis: authors’ reply

Effects of balloon mitral valvuloplasty on systemic and regional left atrial levels of prothrombin fragment 1+2 in mitral stenosis

Effects of balloon mitral valvuloplasty on systemic and regional left atrial levels of prothrombin fragment 1+2 in mitral stenosis

Effects of balloon mitral valvuloplasty on systemic and regional left atrial levels of prothrombin fragment 1+2 in mitral stenosis

A proportion of mitral stenosis patients with left atrial spontaneous echo contrast but without thrombus exhibit a regional hypercoagulable state, characterized by increased left atrial levels, but normal venous levels, of prothrombin fragment 1+2 (F1+2), a marker of thrombin generation. Valve dilatation by balloon mitral valvuloplasty has beneficial effects on left atrial spontaneous echo contrast, but its effect on left atrial thrombin generation is unknown. We examined the effects of balloon mitral valvuloplasty on venous and left atrial levels of F1+2 in 37 patients with mitral stenosis, divided into those with normal (group 1; n=22) and those with increased (group 2; n=15) regional left atrial thrombin generation, as described previously. The mitral valve area increased by a similar degree after the valvuloplasty procedure in the two groups. In group 1, the venous (P<0.005) and left atrial (P<0.0005) levels of F1+2 increased similarly after valvuloplasty, and as a result the left-atrial-venous F1+2 difference was unchanged. The venous F1+2 level also increased after valvuloplasty in group 2 (P<0.005); however, in contrast with group 1, the left atrial level decreased (P<0.03) and as a result the left-atrial-venous difference fell (P<0.05). These results show that balloon mitral valvuloplasty results in an immediate increase in thrombin generation, but a decrease in the left-atrial-venous F1+2 difference, in patients with increased left atrial thrombin generation. The divergent changes in venous and left atrial levels of F1+2 further highlight the limitations of assessing regional changes in coagulation activity by measuring venous levels of coagulation markers.

Increased left atrial thrombin generation in mitral stenosis is not reflected in arterial prothrombin fragment 1+2 levels

A proportion of patients with mitral stenosis have increased left atrial thrombin generation, with elevated left atrial but normal peripheral venous levels of prothrombin fragment 1+2 (F1+2). Whether this pattern of left atrial and venous F1+2 levels is related to limited spillover of F1+2 from the left atrium into the systemic circulation, or to washout of increased left atrial F1+2 production into the arterial circulation with subsequent systemic clearance, is unclear. We examined the relationship between arterial and venous F1+2 levels in mitral stenosis patients without left atrial thrombus. The study group comprised 36 patients with either a normal (n=29) or prolonged (n=7) international normalized ratio (INR; a measure of clotting time) who were undergoing percutaneous balloon mitral valvuloplasty. Baseline arterial and venous blood samples were collected at the beginning of the valvuloplasty procedure, and left atrial and venous samples were collected after trans-septal puncture. The left atrial F1+2 level exceeded the corresponding venous level in patients with a normal INR (P<0.03); however, baseline arterial and venous F1+2 levels were similar. Arterial and venous F1+2 levels were also similar in the subgroup of patients with evidence of a regional increase in left atrial thrombin generation, and were not different from arterial and venous F1+2 levels in patients without such an increase. Baseline arterial and venous F1+2 levels were both lower in the presence of a prolonged INR. Thus the pattern of increased left atrial but normal venous F1+2 levels in mitral stenosis is due to limited spillover from the left atrium into the systemic circulation.

Immediate effect of balloon valvuloplasty on hemostatic changes in mitral stenosis

This study was conducted to assess right and left atrial hemostatic function in patients with mitral stenosis (MS) and to investigate the immediate effect of balloon mitral valvuloplasty (BMV) on hemostatic function. BMV was performed in 28 patients with MS (age 29 ± 8 years) who had sinus rhythm and no left atrial (LA) thrombus. Right and left atrial biochemical markers of platelet activity (platelet factor 4 [PF4] and B thromboglobulin [BTG]), coagulation (thrombin-antithrombin III complex [TAT]), and fibrinolytic activity ( D-dimer) were measured before and 30 minutes after BMV. Right atrial levels of these markers were also measured in 20 control subjects. Compared with control subjects, patients with MS had higher right atrial levels of PF4 (30 ± 15 vs 5 ± 2 IU/ml), BTG (231 ± 53 vs 30 ± 8 IU/ml), TAT (7 ± 4 vs 2 ± 0.3 μg/L), and D-dimer (380 ± 145 vs 160 ± 35 ng/ml, p <0.0001 in all). TAT levels were higher in the left atrium than in the right atrium of patients before BMV (8 ± 4 vs 7 ± 4 μg/L, p <0.0001). BMV was successful (final mitral valve area ≥1.5 cm 2 and ≥50% increase of the initial valve area) in all patients. There was a significant reduction of LA levels of PF4 (35 ± 8 to 26 ± 9 IU/ml, p <0.0001), BTG (225 ± 41 to 196 ± 28 IU/ml, p <0.001), and TAT (10 ± 5 to 7 ± 1 μg/L, p <0.05) in the 16 patients with LA pressure <10 mm Hg after BMV, whereas these markers were not reduced in the 12 patients with left atrial pressure ≥10 mm Hg after BMV. These data indicate that platelet function, coagulation status, and fibrinolytic activity are increased regionally in the left atrium and in the systemic circulation in patients with MS and sinus rhythm in the absence of LA thrombus. Successful BMV induces a significant reduction of prethrombotic status in patients with low LA pressure after the procedure. Patients with high LA pressure after BMV maintain a high prethrombotic state and may be considered at an increased risk of thromboembolism after the procedure.

Amino-terminal proBNP in ovine plasma: evidence for enhanced secretion in response to cardiac overload.

We have recently identified a novel amino-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) in the circulation of humans, the concentration of which increases progressively as the left ventricle fails. To clarify the origins of NT-proBNP in experimental animals, we have developed an RIA for NT-proBNP based on residues 52-71 of ovine proBNP-(1-103) and used it to study cardiac processing, secretion, and metabolism of BNP in sheep with cardiac overload induced by coronary artery ligation (CAL) or rapid left ventricular pacing (rLVP). The concentration of NT-proBNP in left atrial plasma extracts drawn from normal control sheep was threefold that of mature BNP. Size-exclusion and reverse-phase HPLC analyses of plasma extracts coupled to RIA revealed a single peak of immunoreactive (ir) NT-proBNP [ approximately 8,000 relative molecular weight (Mr)], quite distinct from a single peak of ir-mature BNP ( approximately 3,000 Mr). In contrast, ovine cardiac tissue contained only a single immunoreactive peak of high-molecular-weight BNP ( approximately 11,000 Mr), consistent in size with proBNP-(1-103). Sampling from the cardiac coronary sinus in normal control sheep (n = 5) and sheep with CAL (n = 5) revealed that the molar ratio of NT-proBNP to mature BNP was similar. There was a significant gradient of both mature and NT-proBNP across the heart in normal sheep, whereas after CAL the gradient was significant for mature BNP only. In both forms of cardiac overload (CAL and rLVP), left atrial plasma levels of NT-proBNP were significantly increased above normal levels, in contrast with mature BNP levels, which were raised only in the rLVP group of animals. Blockade of natriuretic peptide metabolism in sheep with heart failure (induced by rLVP) raised mature BNP levels threefold but did not affect levels of NT-proBNP. In conclusion, these studies show that NT-proBNP is formed from proBNP stores during secretion and, compared with mature BNP, accumulates in plasma because metabolism of NT-proBNP appears to differ from that of mature BNP. Although its function, if any, remains unclear, plasma NT-proBNP may prove to be a sensitive marker of cardiac overload and/or decompensation.

Angiotensin II receptor gene expression in hypertrophied left ventricles of rat hearts

To examine the expression of angiotensin II AT1a, AT1b and AT2 receptor genes in the left ventricles of rats subjected to ventricular pressure overloading induced by aortic banding for 6 weeks and then 6 weeks medical treatment. Aortic banding was related to an increase in relative weight of the left ventricle from 1.73 +/- 0.06 (sham-operated) to 2.81 +/- 0.25 g/kg, an increase in beta-myosin: alpha-myosin messenger RNA (mRNA) ratio from 0.30 +/- 0.02 to 1.94 +/- 0.55 and an 18-fold increase in left ventricular atrial natriuretic peptide mRNA levels. In contrast, left ventricular pressure overload hypertrophy was not related to a significant change in the abundance of AT1a and AT1b mRNA, which were expressed in a relative ratio of 5:1. Similarly, the abundance of AT2 mRNA was not significantly changed in hypertrophied ventricles. In rats receiving the angiotensin II AT, receptor antagonist losartan (40 mg/kg) for 6 weeks after banding, relative heart weights were 2.39 +/- 0.14 g/kg, the beta-myosin: alpha-myosin ratio was 1.04 +/- 0.20 and atrial natriuretic peptide mRNA levels displayed a blunted increase (11-fold over sham-treated controls), documenting a significant amelioration of left ventricular hypertrophy by blockade of the AT1 receptor. Losartan treatment in parallel did not affect AT1a, AT1b and AT2 receptor mRNA levels, which were not different from those in vehicle-treated or sham-treated controls. These findings confirm that left ventricular hypertrophy in the rat is associated with increased ventricular expression of beta-myosin and of atrial natriuretic peptide and with reduced expression of alpha-myosin. Despite these significant changes in cardiac gene expression no alteration was observed in AT1a, AT1b and AT2 receptor mRNA levels.

Effects of hypertrophy on left atrial and ventricular compliance and plasma ANF levels in conscious dogs.

Alterations in left atrial (LA) and left ventricular (LV) compliance and arterial and coronary sinus atrial natriuretic factor (ANF) concentrations at baseline and in response to both volume depletion and expansion were investigated in 15 conscious dogs with aortic banding-induced LV hypertrophy (LVH) (LV/body wt increased by 64%), which also induced LAH (LA/body wt increased by 61%). With volume expansion coronary sinus ANF increased more (P < 0.05) in dogs with LVH (+427 +/- 88 pg/ml) compared with control dogs (+146 +/- 45 pg/ml). Arterial ANF levels also rose more with volume expansion in LVH. In dogs with LVH, the LV end-diastolic pressure-diameter relationship was shifted to the left with a steeper slope with volume expansion, such that at any given diastolic dimension, diastolic pressure was higher. In contrast, the pressure-dimension relationship for the LA appendage was shifted in the opposite direction during both atrial systolic and diastolic phases, with a more shallow slope in hypertrophy compared with control dogs, resulting in an augmented pressure-dimension product during volume loading in LAH. In conclusion, in dogs with LVH and LAH, enhanced ANF was revealed in the coronary sinus and systemic circulation during volume expansion, which could be due, in part, to a more compliant, but hypertrophied, LA, which responded to equivalent volume loading with an augmented pressure-dimension product.

Pulmonary extraction and left atrial secretion of atrial natriuretic factor during cardiopulmonary bypass surgery

We have investigated the role of the lungs in the extraction of atrial natriuretic factor (ANF) by measuring plasma levels in samples taken from the central circulation in 12 patients (mean age 59 years; range 43 to 68) undergoing cardiac surgery. We also investigated the effects of cardiopulmonary bypass on ANF levels. ANF levels (mean ± SD) were lower in puimonary venous samples (41 ± 20 pg/ml) than in pulmonary arterial samples (54 ± 18 pg/ml; p < 0.001), demonstrating 24% extraction of ANF by the lungs. Both left atrial (47 ± 23 pg/ml) and systemic arterial levels (52 ± 22 pg/ml) were higher than pulmonary venous levels (both p < 0.05), indicating secretion of ANF into the left side of the heart. During cardiopulmonary bypass, plasma ANF concentration fell from 68 ± 23 pg/ml before aortic cross-clamping to 35 ± 13 pg/ml 10 minutes after and 28 ± 9 40 minutes after the application of clamps (both p < 0.001). A rebound rise to 122 ± 33 pg/ml followed the release of the clamp ( p < 0.001). This study demonstrates that ANF is extracted by the lungs and secreted directly into the left side of the heart. The considerable fall in plasma levels that was observed during aortic cross-clamping might contribute to the neurohumoral activation and increased peripheral resistance observed after prolonged cardiopulmonary bypass and to the risk of renal ischemic injury.

Histamine release during paediatric cardiopulmonary bypass

Histamine release occurs during paediatric cardiopulmonary bypass at the time of removal of the aortic cross-clamp. Left atrial histamine levels are significantly (p less than 0.02) higher than right atrial levels at the time of reventilation of the lungs. These results suggest that histamine is released from the pulmonary vasculature following reperfusion.

Age-Related Changes in Basal and Sodium-Stimulated Atrial and Plasma Atrial Natriuretic Factor (ANF) in the Rat

To examine effects of age on basal and sodium-stimulated plasma concentrations and atrial contents of atrial natriuretic factor (ANF), young (2 mo), mature (4 mo), and older adult (12-18 mo) rats were maintained on a low-sodium diet (less than .05% by weight) for 8 days. Half of each group then received a high-sodium diet (3.1%) for 24 hours before sacrifice. Mean plasma ANF concentrations were greater in the older adult rats, 506 +/- 287 pg/ml, than in young or mature rats, 262 +/- 182 and 150 +/- 40 pg/ml, respectively (p less than .001). Age-related increases in plasma ANF concentration and left atrial ANF content (p less than .001) were present in both low- and high-sodium fed rats. Significant differences in plasma and atrial ANF levels between low- and high-sodium fed rats were noted only in older adult rats, where an inverse correlation (r = -.425, p less than .05) was observed between plasma and left atrial ANF levels. These observations demonstrate that plasma and atrial ANF levels increase with age in the rat. With aging, increased ANF effects may modulate other systems regulating cardiovascular homeostasis.