EFFECTS OF FRUSEMIDE AND HYPOXIA ON THE PULMONARY VASCULAR BED IN MAN

Aims Diuretic therapy is conventionally used to treat oedema in patien ts with hypoxic cor pulmonale. This condition is associated with activ ation of the renin angiotensin system (RAS) with elevated levels of an giotensin II (ANG II), a potent pulmonary presser agent. We explored t he 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 stud ied on 2 separate days. They either received 40 mg frusemide daily or placebo for 4 days and were then rendered hypoxaemic, by breathing an N-2/O-2 mixture for 20 min to achieve an SaO(2) of 85-90% adjusted for a further 20 min to achieve an SaO(2) of 75-80%. Pulsed wave doppler echocardiography was used to measure mean pulmonary artery pressure, c ardiac output and hence pulmonary vascular resistance (PVR). Results P lasma renin activity (PRA) was significantly (P<0.01) increased after prior treatment with frusemide compared with placebo at all time point s. 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 SaO of 85-90%: 291 +/- 18 vs 229 +/- 16 dyn s cm(-5) and at SaO(2) of 75-80%: 356 +/- 12 vs 296 +/- 17 dyn s cm(-5) respectively. However, the delta-PVR response to hypoxaemia was not significantly al tered by frusemide compared with placebo. In contrast to its effect on the pulmonary vasculature prior treatment with frusemide did not sign ificantly alter systemic haemodynamic parameters either at baseline or during hypoxia. Conclusions Thus, prior treatment with frusemide incr eased baseline pulmonary vascular resistance and significantly augment ed the hypoxaemic pulmonary vascular response in additive fashion. It is hypothesised that this effect of frusemide may be due to RAS activa tion with ANG II mediated pulmonary vasoconstriction.