saralasin and Lung-Diseases

During our earlier saralasin infusion study in hypertensive patients, we found a drug-induced rise in arterial oxygen tension (PaO2) associated with unchanged mixed venous PO2 or the PaCO2 and unrelated to cardiopulmonary hemodynamic changes. To test the hypothesis that saralasin improved pulmonary mechanics, blood gases, lung mechanics, lung volumes, diffusing capacity, and distribution of ventilation were analyzed and cardiac output (CO) measured in 12 normotensive men with chronic pulmonary disease before and during a 2 1/2 hour infusion of Saralasin (5 micrograms/kg/min). The PaO2 increased from a mean of 63 +/- 3 (SEM) to 70 +/- 3 mm Hg (p less than 0.001), while the CO decreased from 6.81 +/- 0.52 L/min to 6.18 +/- 0.48 L/min (p less than 0.005). The change in (delta)CO correlated with delta PaO2 (r = -0.67, p less than 0.05). Total systemic vascular resistance rose from 1,201 +/- 134 to 1,353 +/- 147 dynes X sec X cm5 (p less than 0.001). The PaCO2 and other measurements remained unchanged. We conclude that saralasin raised the PaO2 not by changing pulmonary function or mechanics, but by redistributing pulmonary blood flow and improving the ventilation-perfusion relationship.

Topics: Adult; Aged; Angiotensin II; Carbon Dioxide; Carbon Monoxide; Cardiac Output; Forced Expiratory Volume; Hemodynamics; Humans; Infusions, Parenteral; Lung; Lung Diseases; Lung Diseases, Obstructive; Male; Middle Aged; Oxygen; Pulmonary Fibrosis; Renin; Saralasin; Sarcoidosis; Vascular Resistance; Vital Capacity

The pulmonary vascular response to breathing low oxygen containing gas mixture was examined before and during Angiotensin II blockade in five open-chested newborn calves. Angiotensin II blockade was achieved by continuous infusion of Sar1-Ile5-Leu8-Angiotensin II (Saralasin), a competitive inhibitor of Angiotensin II. The hypoxic rise in pulmonary vascular resistance after blockade did not differ from that of control. It is concluded that Angiotensin II does not play a significant role in acute hypoxic pulmonary vasoconstriction in the calf.

Topics: Angiotensin II; Animals; Cattle; Hypoxia; Lung; Lung Diseases; Pulmonary Circulation; Saralasin; Vasoconstriction