title: Protamine sulfate causes pulmonary hypertension and edema in isolated rat lungs.
abstract: The polycation protamine sulfate increases microvascular permeability in the kidney by reducing glomerular charge. We have exposed the pulmonary vasculature to protamine sulfate to determine whether electrical charges play a role in protein permeability in lung vascular beds. In anephric rats, protamine sulfate increased hematocrit approximately 25%. With protamine sulfate doses of 0.08 and 0.04 mg/g body wt, lung blood-free wet-to-dry weight ratios were increased (5.24 +/- 0.8 and 4.89 +/- 0.7) compared with control (3.85 +/- 0.3) (P less than 0.05). In isolated, ventilated, and perfused lungs 0.04 mg/g body wt protamine sulfate increased pulmonary arterial pressure from 5.2 +/- 1.4 to 16.3 +/- 3.9 mmHg (P less than 0.01). These lungs gained weight and lung wet-to-dry weight ratios were significantly increased (15.33 +/- 4.26 compared with 6.04 +/- 0.24 for control lungs). Poly-L-lysine, another polycation, also caused significant increases in pulmonary arterial pressure, lung weight, and lung wet-to-dry weight ratios. The addition of diphenhydramine to the perfusate 10 min before the addition of protamine sulfate did not prevent these changes. Heparin (90 U/mg protamine sulfate) reversed the abnormalities. Pulmonary arterial pressure (7.0 +/- 1.1 mmHg) was not significantly different from the control value, lung weight did not increase, and the lung wet-to-dry weight ratio was 6.24 +/- 0.23 (P greater than 0.05). We conclude that polycations have a significant effect on pulmonary vascular resistance and perhaps on permeability.
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability; D004155:Diphenhydramine / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000139:chemically induced*; D066298:In Vitro Techniques; D008297:Male; D011107:Polylysine / Q000494:pharmacology; D011479:Protamines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011652:Pulmonary Circulation; D011654:Pulmonary Edema / Q000139:chemically induced*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D011479:Protamines; D011107:Polylysine; D004155:Diphenhydramine; D006493:Heparin