SUMMARY: Hypoxaemia and angiotensin II both cause pulmonary vasoconstriction and co-exist as pathophysiological pulmonary pressor 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 ( (\boldsymbol{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 \mathrm{~min}\left(\mathrm{~T}{30}\right)), angiotensin II was infused for a further (30 \mathrm{~min}) (until (\mathrm{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_{66}).
The change in MPAP (AMPAP) due to hypoxaemia and angiotensin II together was (18.0 \pm 1.3 \mathrm{mmHg}), significantly greater than the (\triangle) MPAP response to either hypoxaemia alone ((13.4 \pm 1.1 \mathrm{mmHg})) or angiotensin II alone (10.3 (\pm 1.1 \mathrm{mmHg}) ). In terms of change in PVR ( (\triangle \mathrm{PVR})), the response to hypoxaemia and angiotensin II together ( (\mathbf{2 3 0} \pm 25) dyne.s/cm ) was no different from the response to ANG II alone ( (\mathbf{2 1 4} \pm 31) dyne.s/ (/ \mathrm{cm}^{5}) ), although both these were significantly greater than (\triangle P V R) with hypoxaemia alone (114 (\pm 12 \mathrm{dyne} . \mathrm{s} / \mathrm{cm}^{5}) ). The (\triangle M P A P) and (\triangle \mathrm{PVR}) responses to angiotensin II were significantly greater when normoxaemic than when hypoxaemic: (\triangle \mathrm{MPAP}) mean difference (5.6 \mathrm{mmHg}) ( (95 %) confidence interval (CI) 3.0-8.2); (\triangle) PVR mean difference 98 dyne. (/ \mathrm{cm} \mathrm{cm}^{5}(95 % \mathrm{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.