Acute effects of hypoxaemia and angiotensin II in the human pulmonary vascular bed.
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 (T0) 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 (T30), angiotensin II was infused for a further 30 min (until T60). Mean pulmonary artery pressure (MPAP) and total pulmonary vascular resistance (PVR) were determined by pulsed-wave Doppler echocardiography at T0, T30 and T60. 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/cm5) was no different from the response to ANG II alone (214 +/- 31 dyne.s/cm5), although both these were significantly greater than delta PVR with hypoxaemia alone (114 +/- 12 dyne.s/cm5). 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/cm5 (95% CI 16-181). Angiotensin II therefore produced significantly less pulmonary vasoconstriction when hypoxaemic compared with normoxaemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Cargill
R I
RI
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, University of Dundee, Scotland, UK.
Lipworth
B J
BJ
D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D010102:Oxygen Inhalation Therapy; D011652:Pulmonary Circulation / Q000187:drug effects* / Q000502:physiology; D011660:Pulmonary Heart Disease / Q000503:physiopathology / Q000628:therapy; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D000804:Angiotensin II; D012083:Renin