Role of atrial natriuretic peptide in pulmonary permeability and vasoregulation in ovine 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.


METHODS
Prospective experimental investigation.


METHODS
Laboratory at a university hospital.


METHODS
Twelve awake, chronically instrumented sheep.


METHODS
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).


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.


CONCLUSIONS
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.
Stubbe
Henning D
HD
Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Universitätsklinikum Münster, Germany.
Traber
Daniel L
DL
Booke
Michael
M
Traber
Lillian D
LD
Westphal
Martin
M
Van Aken
Hugo
H
Hinder
Frank
F
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000032:analysis / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D008168:Lung / Q000502:physiology*; D008208:Lymphatic System / Q000187:drug effects / Q000502:physiology; D008297:Male; D010539:Permeability / Q000187:drug effects; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology; D011654:Pulmonary Edema / Q000188:drug therapy* / Q000503:physiopathology*; D017461:Receptors, Atrial Natriuretic Factor / Q000037:antagonists & inhibitors*; D012016:Reference Values; D012307:Risk Factors; D012680:Sensitivity and Specificity; D018805:Sepsis / Q000188:drug therapy / Q000382:microbiology; D034561:Sheep, Domestic
D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor