ularitide and Edema

The natriuretic peptide system, which comprises at least four related proteins: atrial natriuretic peptide; brain natriuretic peptide; C-type natriuretic peptide; and urodilatin, exerts important influences on central and renal hemodynamics and renal sodium excretion. Recent studies have examined the role of these peptides in the pathophysiology of edema formation in congestive heart failure, cirrhosis, and nephrotic syndrome and have explored the therapeutic value of manipulating their metabolic pathways. One striking feature appears common to all three states ie, a blunted response to the natriuretic effect of atrial natriuretic peptide, which becomes particularly severe in the late stages of each disease. However, whereas in congestive heart failure and cirrhosis the main mechanism responsible is enhanced proximal tubular reabsorption of sodium resulting in reduced distal sodium delivery to the major site of atrial natriuretic peptide action, in nephrotic syndrome a biochemical defect in the cellular response to atrial natriuretic peptide within the kidney is a more likely explanation. Most information regarding the efficacy of therapies that alter the metabolism or the local action of atrial natriuretic peptide pertain to congestive heart failure. However, continued investigation in this area may ultimately lead to interventions that play a valuable role in the future management of all three edematous states.

Topics: Atrial Natriuretic Factor; Diuretics; Edema; Humans; Natriuresis; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Peptide Fragments; Peptides; Proteins

In the isolated perfused rat lung, perfusion with platelet-activating factor causes bronchoconstriction, vasoconstriction and edema formation. The bronchoconstriction and vasoconstriction are largely mediated by thromboxane, whereas the edema formation is due to enhanced vascular permeability unrelated to eicosanoids. Since natriuretic peptides are known to relax smooth muscle and were suggested to attenuate enhanced vascular permeability, we investigated the effect of urodilatin on the PAF-induced alterations in lung function. Pretreatment with urodilatin (0.25 microM or 0.75 microM) reduced the PAF-induced increase in airway and vascular resistance by approximately 50%. Urodilatin pretreatment, however, was completely ineffective against the PAF-induced increase in weight gain and in vascular permeability, as assessed by the vascular filtration coefficient. Furthermore, urodilatin failed to affect the release of thromboxane into the perfusate in PAF-exposed lungs. Thus, urodilatin relaxes airway and vascular smooth muscle, but fails to reduce edema formation in PAF-perfused rat lungs.

Topics: Analysis of Variance; Animals; Atrial Natriuretic Factor; Bronchoconstriction; Bronchodilator Agents; Capillary Permeability; Edema; Female; Lung; Organ Size; Peptide Fragments; Perfusion; Platelet Activating Factor; Rats; Rats, Wistar; Thromboxanes; Vascular Resistance; Vasoconstriction