OBJECTIVE: Atrial natriuretic peptide is regarded as an important regulator of pulmonary vasomotor tone and permeability. This study investigated the role of atrial natriuretic peptide in sepsis-associated pulmonary pathophysiology. DESIGN: Prospective experimental investigation. SETTING: Laboratory at a university hospital. SUBJECTS: Twelve awake, chronically instrumented sheep. INTERVENTIONS: The sheep were instrumented with lung lymph fistulas and received a continuous infusion with live Pseudomonas aeruginosa for 48 hrs. After 40 hrs, the atrial natriuretic peptide-receptor antagonist HS-142-1 was continuously infused in the HS-124-1 group (3 mg/kg/hr, n = 6) for 8 hrs, whereas the control group received the carrier (n = 6). MEASUREMENTS AND MAIN RESULTS: Lung lymph flow was markedly elevated in response to sepsis after 40 hrs in both groups. Atrial natriuretic peptide-receptor blockade further increased lymph flows by 41 +/- 17% (41 hrs) up to 64 +/- 20% (44 hrs, p < .05) in the presence of normal permeability to protein. Although mean pulmonary artery pressure increased (p < .05 vs. 40 hrs), capillary pressure remained unaffected. Despite identical fluid balances in both groups, cardiovascular filling variables significantly increased in the HS-142-1 group. This was associated with increasing cardiac index and mean arterial pressure (p < .05 vs. 40 hrs). In the control group, all variables remained constant between 41 and 48 hrs. CONCLUSION: Blockade of atrial natriuretic peptide receptors increases pulmonary transvascular fluid flux independent of changes in permeability to protein in chronic ovine sepsis. Atrial natriuretic peptide may therefore play a protective role for the alveolar-capillary barrier during sepsis.
OBJECTIVE:Atrial natriuretic peptide is regarded as an important regulator of pulmonary vasomotor tone and permeability. This study investigated the role of atrial natriuretic peptide in sepsis-associated pulmonary pathophysiology. DESIGN: Prospective experimental investigation. SETTING: Laboratory at a university hospital. SUBJECTS: Twelve awake, chronically instrumented sheep. INTERVENTIONS: The sheep were instrumented with lung lymph fistulas and received a continuous infusion with live Pseudomonas aeruginosa for 48 hrs. After 40 hrs, the atrial natriuretic peptide-receptor antagonist HS-142-1 was continuously infused in the HS-124-1 group (3 mg/kg/hr, n = 6) for 8 hrs, whereas the control group received the carrier (n = 6). MEASUREMENTS AND MAIN RESULTS: Lung lymph flow was markedly elevated in response to sepsis after 40 hrs in both groups. Atrial natriuretic peptide-receptor blockade further increased lymph flows by 41 +/- 17% (41 hrs) up to 64 +/- 20% (44 hrs, p < .05) in the presence of normal permeability to protein. Although mean pulmonary artery pressure increased (p < .05 vs. 40 hrs), capillary pressure remained unaffected. Despite identical fluid balances in both groups, cardiovascular filling variables significantly increased in the HS-142-1 group. This was associated with increasing cardiac index and mean arterial pressure (p < .05 vs. 40 hrs). In the control group, all variables remained constant between 41 and 48 hrs. CONCLUSION: Blockade of atrial natriuretic peptide receptors increases pulmonary transvascular fluid flux independent of changes in permeability to protein in chronic ovine sepsis. Atrial natriuretic peptide may therefore play a protective role for the alveolar-capillary barrier during sepsis.
Authors: Laena Pernomian; Alejandro F Prado; Bruno R Silva; Aline Azevedo; Lucas C Pinheiro; José E Tanus-Santos; Lusiane M Bendhack Journal: Front Physiol Date: 2016-06-23 Impact factor: 4.566