β-Adrenoceptor stimulation of alveolar fluid clearance is increased in rats with heart failure

Abstract

We thus hypothesized that its function might be upregulated in rats with heart failure, a condition that severely challenges the lung's ability to maintain fluid balance. Heart failure was induced by left coronary artery ligation. Echocardiographic and cardiovascular hemodynamics confirmed its development at 16 wk postligation. At that time, alveolar fluid clearance was measured by an increase in protein concentration over 1 h of a 5% albumin solution instilled into the lungs. Baseline alveolar fluid clearance was similar in heart failure and age-matched control rats. Terbutaline was added to the instillate to determine whether heart failure rats responded to ␤-adrenoceptor stimulation. Alveolar fluid clearance in heart failure rats was increased by 194% after terbutaline stimulation compared with a 153% increase by terbutaline in control rats. To determine the mechanisms responsible for this accelerated alveolar fluid clearance, we measured ion transporter expression (ENaC, Na-KATPase, CFTR). No significant upregulation was observed for these ion transporters in the heart failure rats. Lung morphology showed significant alveolar epithelial type II cell hyperplasia in heart failure rats. Thus, alveolar epithelial type II cell hyperplasia is the likely explanation for the increased terbutaline-stimulated alveolar fluid clearance in heart failure rats. These data provide evidence for previously unrecognized mechanisms that can protect against or hasten resolution of alveolar edema in heart failure. albumin; terbutaline APPROXIMATELY FIVE MILLION Americans are living with heart failure, with 400,000 new cases diagnosed annually (18). A major clinical problem in heart failure is the development of pulmonary venous (and consequently, pulmonary capillary) hypertension, which ultimately may lead to pulmonary edema and impaired blood oxygenation. Recent studies have demonstrated that excess pulmonary edema fluid is cleared from the alveoli secondary to active transepithelial Na transport (14, 31). The alveolar epithelium plays a critical role during pulmonary edema recovery by actively absorbing Na (14, 31). ␤-adrenoceptor and dopamine receptor agonists increase Na transport and thus hasten the resolution of pulmonary edema (2, 6, 31). These observations have important clinical significance because they suggest that ␤-adrenoceptor-or dopamine receptor-agonist therapy might help patients to recover more rapidly from pulmonary edema (2, 16).Lungs of heart failure patients undergo extensive remodeling (18,25,26), resulting in architectural changes such as pulmonary artery and vein wall thickening, pulmonary arteriole muscularization, and capillary endothelial and alveolar epithelial basement membrane thickening (18). Collectively, such remodeling results in increased alveolocapillary barrier thickness, correlating with reduced microvascular fluid and protein permeabilities (11,20,45). In addition to the aforementioned changes, alveolar epithelial type II cell proliferation may occur in these lungs (25,26). Hence, the hypot...

Increased renal ENaC subunits and sodium retention in rats with chronic heart failure

“…This distal nephron activation of renin-ANG II-ENaC system may also play an important role in the renal pathophysiology of CHF. It is of interest to note that the changes reported in the present study are specific to the kidney, since expression of ENaC in the lungs of rats with CHF is not altered (17).…”

Relationship between the Autoantibody and Expression of β3-Adrenoceptor in Lung and Heart

“…Recently, the research has found that the administration of an inhaled β 2 -AR agonist can improve pulmonary function in patients with congestive heart failure, thus suggesting the involvement of β 2 -AR [14]. Other studies have found that β 2 -agonist can increase alveolar fluid clearance in rats with heart failure [15]; however, the other 2 subtypes (β 1 -AR and β 3 -AR) in pulmonary tissues have gained less attention. Recent research has demonstrated very low expression of β 3 -AR mRNA in the lungs, and the authors have suggested that the expression of β 3 -AR mRNA could probably be accounted for by the presence of fat [16].…”

Alveolar Epithelium and Fluid Transport

“…Studies of fluid clearance have been done in intubated, ventilated patients by measuring the concentration of total protein in sequential samples of undiluted pulmonary edema fluid aspirated from the distal air spaces of the lung with a standard suction catheter passed through the endotracheal tube into a wedged position in the distal airways of the lung. 39,71,72 This method for measuring fluid clearance in patients was adapted from the method for aspirating fluid from the distal air spaces of the lung in experimental studies in small and large animals. 5,8 The clinical procedure has been validated in patients by demonstrating that there is a relationship between fluid clearance and the improvement in oxygenation and the chest radiograph.…”

“…In a recent study of congestive heart failure in rats, it was demonstrated that β-adrenergic stimulation increased alveolar fluid clearance and that type II cell hyperplasia might be responsible for the stimulation. 71 The majority of patients with increased permeability edema and acute lung injury (ALI) have impaired alveolar epithelial fluid transport, a finding that is associated with more prolonged respiratory failure and a higher mortality ( Fig. 9-2).…”