Abstract 389: Human Cardiac Sympathetic Nerves Switch the Neurotransmitter Property from Catecholaminergic to Cholinergic in Patients with Severe Heart Failure

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Hideaki Kanazawa ◽  
Masaki Ieda ◽  
Kensuke Kimura ◽  
Takahide Arai ◽  
Haruko Manabe ◽  
...  
Keyword(s):  
Heart Failure ◽  
Interstitial Fibrosis ◽  
Severe Heart Failure ◽  
Sympathetic Nerves ◽  
Cholinergic Neuron ◽  
Heart Weight ◽  
Control Group ◽  
Down Regulation ◽  
Stellate Ganglia ◽  
Nerve Bundles

[Background] Congestive heart failure (CHF) is characterized by activation of the sympathetic nervous system (SNS) with depletion of norepinephrine (NE) stores, which was initially considered to be the result of excess NE secretion and the loss of noradrenergic nerve terminals. Recent studies however have revealed that it is caused by down regulation of NE synthesis and re-uptake, although the molecular mechanism of down regulation of the sympathetic neuronal function remains unknown. We recently found in an animal model of CHF that the cardiac SNS switches the neurotransmitter property from catecholaminergic to cholinergic, mediated by cytokines LIF and CT-1 secreted from failing myocardium. This study was designed to investigate whether or not this cholinergic transdifferentiation of cardiac SNS occurs in patients with CHF. [Methods & Results] (1) We analyzed 8 samples from patients who died of non-cardiac causes obtained at autopsy (control group), and 8 samples from patients with CHF (CHF group). Five of them died of CHF, and 3 were obtained from native hearts of transplant recipients. (2) The heart weight was significantly higher in the CHF group. (3) The gross morphology of the cardiac SNS did not differ between the two groups. HE and Masson trichrome staining showed disorganized cardiomyocytes and interstitial fibrosis in CHF. (4) Immunostaining for tyrosine hydroxylase (TH, sympathetic nerve marker) revealed that the epicardial nerve bundles and stellate ganglia of the control group had a predominance of TH + nerves, whereas those of CHF group were significantly decreased. (5) Immunostaining for choline transporter (CHT, cholinergic neuron marker) revealed that CHT + neurons were markedly increased in the epicardial nerve bundles of CHF hearts compared with the control group. Some nerves co-expressed both TH and CHT markers. (6) Immunostaining for choline acetyl transferase (ChAT, a cholinergic neuron marker) revealed that stellate ganglia had a lot of ChAT + neurons compared with the control. (7) Nissl staining showed that there was no difference between the two groups in neuron number in the stellate ganglia. [Conclusions] These results indicated that in patients with CHF the cardiac sympathetic nerves also had cholinergic nerve properties.

The use of peripherally inserted central catheter reduced the incidence of phlebitis in heart failure patients: A randomized trial

2021 ◽  
pp. 112972982110596
Author(s):  
Eunice Vieira Cavalcante Silva ◽  
Marcelo Eidi Ochiai ◽  
Kelly Regina Novaes Vieira ◽  
Antonio Carlos Pereira Barretto
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Severe Heart Failure ◽  
Decompensated Heart Failure ◽  
Venous Access ◽  
Control Group ◽  
Control Groups ◽  
Heart Failure Patients ◽  
Peripheral Venous Access ◽  
And Control

Background: During decompensated heart failure, the use of intravenous inotropes can be necessary. With peripheral venous access, prolonged inotrope infusion can cause phlebitis. However, traditional central venous catheters have possible complications. Peripherally inserted central catheters (PICCs) may be an alternative to traditional catheters. Aim: Our objective was to compare the incidence of phlebitis between patients with PICC and those with peripheral venous access catheter indwelling. Methods: In a randomized clinical trial, the patients were randomized to PICC and control groups, with 40 patients in each group. The inclusion criteria were hospitalized patients with advanced heart failure, ejection fraction of <0.45, and platelet count of >50,000/mm3 and current use of continuous intravenous infusion of dobutamine. The patients were randomly assigned to receive a PICC or keep their peripheral venous access. The primary end point was the occurrence of phlebitis. Results: The PICC and control groups included 40 patients each. The median age was 61.5 years; ejection fraction, 0.24; and dobutamine dose, 7.73 µg/(kg min). Phlebitis occurred in 1 patient (2.5%) in the PICC group and in 38 patients (95.0%) in the control group, with an odds ratio of 0.10% (95% confidence interval: 0.01%–1.60%, p < 0.001). Conclusion: In conclusion, in severe heart failure patients who received intravenous dobutamine, PICC use reduced the incidence of phlebitis when compared to patients with peripheral venous access. Therefore, the PICC use should considered over peripheral venous access for prolonged intravenous therapy in heart failure patients.

Abstract 744: Arrhythmogenesis in Heart Failure: Role of Interstitial Fibrosis

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Jorge E Massare ◽  
R. Haris Naseem ◽  
Jeff M Berry ◽  
Farhana Rob ◽  
Joseph A Hill
Keyword(s):  
Heart Failure ◽  
Interstitial Fibrosis ◽  
Systolic Dysfunction ◽  
Ventricular Tachyarrhythmia ◽  
Severe Heart Failure ◽  
Pressure Overload ◽  
Cellular Events ◽  
Action Potential Prolongation

Background: Sudden cardiac death due to ventricular tachyarrhythmia (VT) accounts for a large number of deaths in patients with heart failure. Several cellular events which occur during pathological remodeling of the failing ventricle are implicated in the genesis of VT, including action potential prolongation, dysregulation of intercellular coupling, and fibrosis. Interestingly, transgenic mice over-expressing constitutively active PKD (caPKD) develop severe heart failure without interstitial fibrosis, an otherwise prominent feature of the disease. The goal here was to define the role of interstitial fibrosis in the proarrhythmic phenotype of failing myocardium. Methods and Results: We performed echocardiographic, electrocardiographic, and in vivo electrophysiologic studies in 8 –10 week old caPKD mice (n=12). Similar studies were performed in mice with load-induced heart failure induced by surgical pressure overload (sTAB, n=10), a model of heart failure with prominent interstitial fibrosis. caPKD and sTAB mice showed similar degrees of ventricular dilation (LV systolic dimension caPKD 2.4±0.8 mm vs 3.0±0.9 sTAB, p=0.18) and severe systolic dysfunction (% fractional shortening caPKD 25±11 vs 28±11 sTAB, p=0.62). Yet, caPKD mice showed minimal interstitial fibrosis, comparable to unoperated controls. With the exception of ventricular refractory period, which was higher in caPKD (48±11 msec vs 36±7 TAB and 40±8 WT, p<0.05), other electrocardiographic and electrophysiologic variables were similar among the 3 groups (p=NS), including heart rate, QT duration, and mean VT threshold. As expected, VT (≥3beats) was readily inducible by programmed stimulation in sTAB mice (7/10). By contrast, VT was less inducible in caPKD mice (4/12; p=0.1 vs TAB and <0.05 vs WT), and uninducible in unoperated controls (0/12). VT was polymorphic in both models, but episodes of VT were both slower (VT cycle length caPKD 58±4.0 msec vs 48±1 sTAB, p=0.016) and longer in caPKD mice (caPKD 1.8±0.7 sec vs 0.47±0.3 sTAB, p=0.038). Conclusion: Interstitial fibrosis contributes to the inducibility, maintenance, and rate of VT in heart failure. These findings highlight the importance of anti-remodeling therapies known to target fibrosis in heart disease.

Regional epinephrine kinetics in human heart failure: evidence for extra-adrenal, nonneural release

1995 ◽  
Vol 269 (1) ◽  
pp. H182-H188 ◽  
Author(s):  
D. M. Kaye ◽  
J. Lefkovits ◽  
H. Cox ◽  
G. Lambert ◽  
G. Jennings ◽  
...  
Keyword(s):  
Heart Failure ◽  
Release Rate ◽  
Mental Arithmetic ◽  
Sympathetic Neurons ◽  
Severe Heart Failure ◽  
Sympathetic Nerves ◽  
Whole Body ◽  
Plasma Epinephrine ◽  
Human Heart Failure ◽  
Arterial Plasma

A number of neurohumoral processes are activated in heart failure, including an increase in the plasma concentration of epinephrine. Radiotracer methods were applied in 42 patients with severe heart failure and 31 healthy volunteers to ascertain the rate at which epinephrine is released to plasma and to evaluate the contribution of extra-adrenal sources. The increase in arterial plasma epinephrine observed in the heart failure patients was explained principally by a 34% (P < 0.001) reduction in the whole body clearance rate of epinephrine from plasma. Regional venous sampling from the heart, lungs, and hepatomesenteric beds was performed in a subgroup of the study population, revealing a significant increase in the release rate of epinephrine to plasma from these organs in heart failure which accounted for 26% of the whole body plasma epinephrine appearance rate. To establish whether the cardiac epinephrine release was of neuronal origin, a physical (cycling) or mental (difficult mental arithmetic) stressor was applied as a sympathoexcitatory stimulus, given that a proportional release of norepinephrine and epinephrine could be expected if sympathetic nerves were the source. These interventions caused significant increases in the regional spillover of norepinephrine to plasma but not that of epinephrine. These findings suggest that nonadrenal tissues contribute significantly to the whole body epinephrine release rate in heart failure and that this may arise from a site other than sympathetic neurons.

scholarly journals Cardiac Contractility Modulation Attenuates Chronic Heart Failure in a Rabbit Model via the PI3K/AKT Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Qingqing Hao ◽  
Feifei Zhang ◽  
Yudan Wang ◽  
Yingxiao Li ◽  
Xiaoyong Qi
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Cardiac Contractility ◽  
Rabbit Model ◽  
The Body ◽  
Heart Weight ◽  
Akt Pathway ◽  
Control Group ◽  
Cardiac Contractility Modulation ◽  
Positive Effects

The Akt plays an important role in regulating cardiac growth, myocardial angiogenesis, and cell death in cardiac myocytes. However, there are few studies to focus on the responses of the Akt pathway to cardiac contractility modulation (CCM) in a chronic heart failure (HF) model. In this study, the effects of CCM on the treatment of HF in a rabbit model were investigated. Thirty six-month-old rabbits were randomly separated into control, HF, and CCM groups. The rabbits in HF and CCM groups were pressure uploaded, which can cause an aortic constriction. Then, CCM was gradually injected to the myocardium of rabbits in the CCM group, and this process lasted for four weeks with six hours per day. Rabbit body weight, heart weight, and heart beating rates were recorded during the experiment. To assess the CCM impacts, rabbit myocardial histology was examined as well. Additionally, western blot analysis was employed to measure the protein levels of Akt, FOXO3, Beclin, Pi3k, mTOR, GSK-3β, and TORC2 in the myocardial histology of rabbits. Results showed that the body and heart weight of rabbits decreased significantly after suffering HF when compared with those in the control group. However, they gradually recovered after CCM application. The CCM significantly decreased collagen volume fraction in myocardial histology of HF rabbits, indicating that CCM therapy attenuated myocardial fibrosis and collagen deposition. The levels of Akt, FOXO3, Beclin, mTOR, GSK-3β, and TORC2 were significantly downregulated, but Pi3k concentration was greatly upregulated after CCM utilization. Based on these findings, it was concluded that CCM could elicit positive effects on HF therapy, which was potentially due to the variation in the Pi3k/Akt signaling pathway.

scholarly journals Ophiopogon japonicas (Linn. f.) Ker-Gawl. extract ameliorates chronic heart failure in rats

2021 ◽  
Vol 18 (9) ◽  
pp. 1853-1857
Author(s):  
Hu-zhi Cai ◽  
Yan-ping Tang ◽  
Xin-yu Chen ◽  
Hai-bo Xie ◽  
Qing-yang Chen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Normal Control Group ◽  
Heart Weight ◽  
Control Group ◽  
High Dose ◽  
Chronic Congestive Heart Failure ◽  
Whole Heart

Purpose: To investigate the effect of Ophiopogon japonicas (Linn. f.) Ker-Gawl. extract (OJKE) on oxidative stress and hemodynamics in chronic congestive heart failure (CHF) rats. Methods: The rats were modelled to congestive heart failure (except normal group) , and then randomly divided into normal control group, model (untreated) group, captopril group, high-dose, middle-dose and low-dose of OJKE groups. They were treated for 4 weeks as appropriate for each group. At the end of treatment, the hemodynamic function, whole heart weight index, and blood creatinine kinase (CK), as well as superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), nitricoxide synthase (NOS) were determined. Results: Compared with the normal control group, arterial systolic pressure (SBP), diastolic pressure (DBP), mean arterial pressure (MAP), heart rate (HR), left ventricular systolic peak (LVSP), and left ventricular pressure change rate (dp/dt max) significantly decreased (p < 0.05), while left ventricular end diastolic pressure (LVEDP), whole heart weight index, blood CK, MDA, NO, NOS significantly increased in the untreated group (p < 0.05). A high dose of OJKE significantly improved hemodynamic function, lowered MDA (8.33 ± 2.12 nmol/mL) and NO (20.58 ± 3.53 umol/L) levels (p < 0.05), and also decreased CK (0.53±0.37 U/mL) and NOS (22.46±3.29 U/mL) in CHF rats (p < 0.05). Conclusion: OJKE improved adriamycin-induced chronic congestive heart failure in rats significantly.

Abstract 181: Cardiac Hypertrophy And Heart Failure In K-channel Ancillary Subunit Depleted Mice

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Torsten K Roepke ◽  
Ulrike Lisewski ◽  
Leonhard Schleussner ◽  
Carolin Gaertner ◽  
Clemens Koehncke
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Potassium Channel ◽  
Isolated Heart ◽  
Severe Heart Failure ◽  
Calcium Handling ◽  
K Channel ◽  
Sodium Calcium Exchanger ◽  
Down Regulation ◽  
And Function

Down regulation of cardiac K+ currents has been described in hypertrophic heart disease and heart failure. However, so far no mutations in potassium channel genes have been found in patients with cardiac hypertrophy/heart failure. It therefore remains controversial whether K+ current down regulation represents a primary cause of cardiac hypertrophy/heart failure or epiphenomena. KCNE2 is a voltage gated potassium channel ancillary subunit that is associated with inherited and acquired long QT syndrome. We recently developed KCNE2-/- mice. KCNE2-/- mice have normal cardiac morphology and function at 3-6 months of age despite a repolarization defect caused by disruption of IKslow, 1 and Ito, f. However, aged KCNE2-/- mice (12 months and older) develop significant cardiac hypertrophy and severe heart failure assessed by echocardiography, isolated heart (Langendorff) and reduced cellular shortening (IonOptix). Furthermore, after Angiotensin II stimulation 3-6 months old KCNE2-/- mice also develop significant cardiac hypertrophy and fibrosis compared to age-matched KCNE2+/+ siblings. Taqman PCR revealed molecular remodelling in hypertrophied failing KCNE2-/- hearts with induction of the fetal gene program (ANF re-expression), significant up regulation of Sodium-Calcium Exchanger (NCX) and significant down regulation of phospholamban. Alterations in Calcium handling proteins were also recapitulated on protein level by Western Blotting. Furthermore, electrophysiological studies by patch clamp analysis of isolated cardiomyocytes revealed a decrease in current densities of the L-type Ca2+-current and a strongly diminished response to isoprenaline stimulation in hypertrophied failing KCNE2-/- cardiomyocytes. We therefore conclude that primary disruption of repolarizing Kv currents by KCNE2 deletion leads to altered Calcium handling and consecutive induction of cardiac hypertrophy/heart failure.

Effect of Zhen-wu decoction on chronic heart failure in rats

2017 ◽  
Vol 16 (10) ◽  
pp. 2439-2443
Author(s):  
Zhongyong Liu ◽  
Lin Li ◽  
Shihua Luo ◽  
Jia Fang
Keyword(s):  
Heart Failure ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Normal Control Group ◽  
Heart Weight ◽  
Control Group ◽  
High Dose ◽  
Chronic Congestive Heart Failure ◽  
Hemodynamic Function ◽  
Whole Heart

Purpose: To investigate the effect of Zhen-wu decoction (ZWD) on oxidative stress and hemodynamics in chronic congestive heart failure (CHF) rats.Methods: After Sprague Dawley (SD) rats were successfully prepared into CHF, they were randomly divided into normal control group, model (untreated CHF) group,  captopril group, high-dose, middledose and low-dose of ZWD groups, and were  treated with drugs for 4 weeks respectively. At the end of the experiment,  hemodynamic function, whole heart weight index, blood creatinine kinase (CK), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO) and nitric oxide synthase (NOS) were determined.Results: Compared with normal control group, ZWD group showed decreased arterial systolic pressure (SBP, 89.16 ± 17.27 mmHg), diastolic pressure (DBP, 72.54 ± 22.36 mmHg), mean arterial pressure (MAP, 72.64 ± 11.87 mmHg), heart rate (HR, 368.25 ± 39.12 beats/min), left ventricular systolic peak (LVSP, 105.27 ± 15.23 mmHg), and left ventricular pressure change rate (dp/dt max) (p < 0.05), while left ventricular end diastolic pressure (LVEDP) (19.52 ± 1.89 mmHg), whole heart weight index (2.74 ± 0.16 mg/g), blood CK (0.98 ± 0.16 U/mL), MDA (17.28 ± 2.94 nmol/mL), NO (36.35 ± 3.27 umol/L), NOS (39.89 ± 3.56 U/mL) significantly  increased (p < 0.05). High dose of ZWD significantly improved hemodynamic  function, lowered MDA (8.85 ± 2.14 nmol/mL) and NO (24.25 ± 3.21 umol/L) levels (p < 0.05), and also decreased CK (0.58 ± 0.37 U/mL) and NOS (26.12 ± 3.87 U/mL) in CHF rats (p < 0.05).Conclusion: ZWD improves adriamycin-induced chronic congestive heart failure in rats significantly, and therefore has potential to be developed for the management of chronic congestive heart failure.Keywords: Zhen-wu decoction, Chronic heart failure, Hemodynamic function,  Oxidative stress

Effect of transplantation of cord blood total nucleated cells on the manifestation and prognosis of refractory congestive heart failure

2016 ◽  
Vol 4 (1) ◽  
pp. 10-13
Author(s):  
O. Usenko ◽  
A. Yakushev ◽  
M. Kostylyev ◽  
V. Onischenko
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Cord Blood ◽  
Exercise Tolerance ◽  
Severe Heart Failure ◽  
Functional Class ◽  
Control Group ◽  
Observation Study ◽  
Death Risk ◽  
Increased Risk

The results of a prospective non-randomized observation study without control group to assess the course of heart failure in patients who underwent of cord blood total nucleated cells (CB TNCs) transplantation combined with traditional drug therapy have been presented. Materials. The study included 20 patients with congestive heart failure (CHF) IIA-IIB stage, functional class III-IV by the NYHA. CB TNCs transplantation was performed by a single intravenous dose of cell product "Cryopreserved human cord blood". Before and 1, 3, 6 and 9 months after CB TNC transplantation patients underwent echocardiographic study, the results of tests with the 6-minute walk determined exercise tolerance. The concentration of brain natriuretic peptide precursor (NT-proBNP) in blood was determined. The cardiovascular death risk was calculated using the scale MAGGIC. Results. Initial patients’ status was characterized by the presence of severe heart failure with reduced contractility of the myocardium and increased risk of 1- and 3-year death. Traditional conservative therapy (beta blockers, ACE inhibitors, diuretics) was not effective. After CB TNC transplantation there was registered a significant improvement of general condition of patients, an increase in exercise tolerance and, therefore, reduce of HF functional class by NYHA (before transplantation average FC was 3.2, in the post-transplant period – from 2.1 to 2, 8). Also after TNCs transplantation levels of biochemical markers of HF significantly decreased (before CB TNCs transplantation the level of NT-proBNP was 2370.3 ± 448.9 pg/mL, after CB TNCs transplantation – from 1198,6 ± 396,3 to 2300,7 ± 403,0 pg/mL ) and the same was estimated death risk from HF (1-year – 10.1-37.4 %, 3 years - 9.1-42.3 % relative to the data of the initial state). Reduced HF manifestations after CB TNCs transplantation allowed to reduce significantly the diuretics dose. Conclusion. Thus, transplantation of cord blood total nucleated cells in complex treatment of congestive heart failure has led to a greater efficiency of therapy and a significant reduce of CHF manifestations in patients.

scholarly journals Assessment of Pharmacist Intervention Among Post Hospital Discharge Patients with Moderate and Severe Acute Heart Failure

2019 ◽  
pp. 50-60
Keyword(s):  
Quality Of Life ◽  
Heart Failure ◽  
Medication Adherence ◽  
Acute Heart Failure ◽  
Hospital Readmission ◽  
Severe Heart Failure ◽  
Pharmacist Intervention ◽  
Control Group ◽  
Moderate Heart Failure

Background: Acute heart failure is the most common cause for hospitalization and the third highest cause of hospital readmission with nearly quarter of patients being re hospitalized within 30 days after discharge. Implementation of Clinical pharmacists in coordinated inpatient care, discharge planning and outpatient care result in significant improvements in adverse drug events reduction, medication adherence, quality of life and patient knowledge. Objective: Evaluating pharmacist- based program for patients with moderate and sever acute heart failure via improving summary discharge in reduction hospital readmission, enhancing medications adherence and improve quality of life. Patients and Methods: This prospective study was carried out under interventional pharmacist- based program carried out on 50 patients whom completed this study, they were randomly allocated to two groups, program group who are receiving program for assessment and review starting from 30 minutes pre hospital discharge till 12 weeks. The control group on usual care which include physician-based discharge summary, routine laboratory test without pharmacist intervention (25 patients for each group). Result: After 12 weeks of follow up among program patients in comparison with control group, study findings revealed significant improvement in self-care heart failure index domains (maintenance, management, confidence and total SCHFI score (P=0.001) in both moderate heart failure (NYHAIII) and severe heart failure (NYHAIV) groups, also increase in domains of belief medication questionnaire whether specific necessity and specific concern domains (P=0.001) or decreased in general harm and general overuse (P=0.001) in both moderate and severe heart failure. Moreover, increase in all domains of WHO quality of life questionnaire (WHOQOL) (P=0.001) in both moderate and sever heart failure with predominant improvement in moderate heart failure. Both serum brain natriuretic peptide (P=0.001) and cardiac troponin I (P<0.01) level were decreased in patients with moderate and severe HF and ejection fraction was improved (P=0.03) only among patients with severe HF of program group. Conclusion: Implementing pharmacist- based management program for patients with moderate and severe acute heart failure via summary discharge markedly improve disease awareness, medication adherence, reduced hospital readmission and total mortality at the end-line of study among intervention patients compared to the usual care.

Divergent regulation of atrial natriuretic factor receptors in high-output heart failure

1992 ◽  
Vol 263 (6) ◽  
pp. H1790-H1797 ◽  
Author(s):  
R. Garcia ◽  
M. C. Bonhomme ◽  
E. L. Schiffrin
Keyword(s):  
Heart Failure ◽  
Atrial Natriuretic Factor ◽  
Heart Weight ◽  
Control Group ◽  
Receptor Density ◽  
Natriuretic Factor ◽  
Shunt Group ◽  
High Output Heart Failure ◽  
High Output ◽  
Atrial Natriuretic

We have investigated whether binding parameters and subtypes of glomerular, papillary, and vascular atrial natriuretic factor (ANF) receptors differ in rats with moderate high-output heart failure [aortocaval (AC) shunt] from their sham-operated controls. Body weight was lower and relative heart weight was higher in the AC shunt group than in the control group. Plasma renin activity (PRA) was also greater in AC shunt rats. Plasma COOH- and NH2-terminal ANF levels were higher in AC shunt animals than in their control counterparts. Total atrial ANF content was elevated in both the right and left atria of the AC shunt group. Glomerular and papillary ANF receptor density (Bmax) and ANF receptor affinity (Kd) were similar in both AC shunt and control rats. Vascular ANF receptor density and affinity were lower in AC shunt (Bmax = 65 +/- 13 fmol.mg protein; Kd = 467 +/- 52 pM) than in control rats (Bmax = 188 +/- 34 fmol.mg protein; Kd = 278 +/- 11 pM). Irreversible cross-linking of 125I-labeled ANF followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions and radioautography demonstrated that both high- and low-molecular weight receptors were unchanged in glomerular membranes and downregulated in vascular membranes from AC shunt animals. However, guanosine 3',5'-cyclic monophosphate (cGMP) production by the isolated glomeruli of AC shunt rats was lower than that of controls. We conclude that in the presence of elevated plasma ANF levels, glomerular, papillary, and vascular ANF receptors may be regulated differently.

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