ACUTE EFFECTS OF HYPOXEMIA AND ANGIOTENSIN-II IN THE HUMAN PULMONARY VASCULAR BED

Hypoxaemia and angiotensin II both cause pulmonary vasoconstriction and co-exist as pathophysiological pulmonary presser stimuli in patients with cor pulmonale. Evidence from animal studies, however suggests that angiotensin II may modulate the hypoxic pulmonary vasoconstrictor response. We have therefore studied how hypoxaemia and angiotensin II interact in the human pulmonary vascular bed. Eight male volunteers were studied on two occasions. From baseline (T-0) onwards, subjects breathed room air at one visit, and on the other, a nitrogen/oxygen mixture which rendered arterial oxygen saturation between 75% and 80%. After 30 min (T-30), angiotensin II was infused for a further 30 min (until T-60). Mean pulmonary artery pressure (MPAP) and total pulmonary vascular resistance (PVR) were determined by pulsed-wave Doppler echocardiography at T-0, T-30 and T-60. The change in MPAP (Delta MPAP) due to hypoxaemia and angiotensin II together was 18.0+/-1.3 mmHg, significantly greater than the Delta MPAP response to either hypoxaemia alone (13.4+/-1.1 mmHg) or angiotensin II alone (10.3+/-1.1 mmHg). In terms of change in PVR (Delta PVR), the response to hypoxaemia and angiotensin II together (230+/-25 dyne.s/cm(5)) was no different from the response to ANG II alone (214+/-31 dyne.s/cm(5)), although both these were significantly greater than Delta PVR with hypoxaemia alone (114+/-12 dyne.s/cm(5)). The Delta MPAP and Delta PVR responses to angiotensin II were significantly greater when normoxaemic than when hypoxaemic: Delta MPAP mean difference 5.6 mmHg (95% confidence interval (CI) 3.0-8.2); Delta PVR mean difference 98 dyne.s/cm(5) (95%CI 16-181). Angiotensin II therefore produced significantly less pulmonary vasoconstriction when hypoxaemic compared with normoxaemia. This suggests that in patients with cor pulmonale, alleviating hypoxaemia with oxygen therapy could allow angiotensin II to have proportionately greater pulmonary vasoconstrictor effects.