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Effects of frusemide and hypoxia on the pulmonary vascular bed in man
Author(s) -
Kiely David G.,
Cargill Robert I.,
Lipworth Brian J.
Publication year - 1997
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.1997.00553.x
Subject(s) - hypoxic pulmonary vasoconstriction , medicine , diuretic , furosemide , hypoxia (environmental) , pulmonary artery , pulmonary hypertension , vascular resistance , placebo , cardiology , hemodynamics , renin–angiotensin system , vasoconstriction , anesthesia , cardiac output , blood pressure , chemistry , oxygen , pathology , alternative medicine , organic chemistry
Aims 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 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, 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 SaO 2 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 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.