Effects of frusemide and hypoxia on the pulmonary vascular bed in man.
OBJECTIVE
Diuretic therapy is conventionally used to treat oedema in patients with hypoxic cor pulmonale. This condition is associated with activation of the renin angiotensin system (RAS) with elevated levels of angiotensin II (ANG II), a potent pulmonary pressor agent. We explored the hypothesis that RAS activation by diuretic therapy might therefore worsen hypoxic pulmonary vasoconstriction via the effects of ANG II on the pulmonary vascular bed.


METHODS
Eight normal volunteers were studied on 2 separate days. They either received 40 mg frusemide daily or placebo for 4 days and were then rendered hypoxaemic, by breathing an N2/O2 mixture for 20 min to achieve an SaO2 of 85-90% adjusted for a further 20 min to achieve an SaO2 of 75-80%. Pulsed wave doppler echocardiography was used to measure mean pulmonary artery pressure, cardiac output and hence pulmonary vascular resistance (PVR).


RESULTS
Plasma renin activity (PRA) was significantly (P < 0.01) increased after prior treatment with frusemide compared with placebo at all time points. Prior treatment with frusemide significantly (P < 0.05) increased PVR compared with placebo at baseline: 185 +/- 17 vs 132 +/- 10 dyn s cm-5 at an SaO2 of 85-90%: 291 +/- 18 vs 229 +/- 16 dyn s cm-5 and at SaO2 of 75-80%: 356 +/- 12 vs 296 +/- 17 dyn s cm-5 respectively. However, the delta-PVR response to hypoxaemia was not significantly altered by frusemide compared with placebo. In contrast to its effect on the pulmonary vasculature prior treatment with frusemide did not significantly alter systemic haemodynamic parameters either at baseline or during hypoxia.


CONCLUSIONS
Thus, prior treatment with frusemide increased baseline pulmonary vascular resistance and significantly augmented the hypoxaemic pulmonary vascular response in additive fashion. It is hypothesised that this effect of frusemide may be due to RAS activation with ANG II mediated pulmonary vasoconstriction.
Kiely
D G
DG
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, University of Dundee, UK.
Cargill
R I
RI
Lipworth
B J
BJ
D000328:Adult; D000704:Analysis of Variance; D004232:Diuretics / Q000494:pharmacology*; D015150:Echocardiography, Doppler; D004573:Electrolytes / Q000097:blood; D005665:Furosemide / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D011652:Pulmonary Circulation / Q000187:drug effects* / Q000502:physiology; D012083:Renin / Q000097:blood
D004232:Diuretics; D004573:Electrolytes; D005665:Furosemide; D012083:Renin