Chest
Volume 109, Issue 2, February 1996, Pages 424-429
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Clinical Investigations: Vascular
Lisinopril Attenuates Acute Hypoxic Pulmonary Vasoconstriction in Humans

https://doi.org/10.1378/chest.109.2.424Get rights and content

Objective

We have studied the effects of angiotensin-converting enzyme (ACE) inhibition with lisinopril on acute hypoxic pulmonary vasoconstriction (HPV).

Design

Randomized, double-blind, placebo-controlled study in ten healthy volunteers. Subjects received four daily doses of lisinopril or matched placebo before attending the laboratory 5 h after taking the final dose. After reaching a resting hemodynamic state, subjects were made hypoxemic (SaO2,75 to 80%) for 30 min.

Measurements

Pulmonary and systemic hemodynamic parameters were measured noninvasively at baseline and after 30 min of hypoxemia.

Results

Mean pulmonary artery pressure (MPAP) and total pulmonary vascular resistance (TPR) were similar at baseline on both study days. The increase in MPAP induced by hypoxemia was significantly blunted by pretreatment with lisinopril (means and 95% confidence interval [CI] for difference) 13.4 mm Hg vs placebo 19.6 mm Hg (95% CI, 2.5, 9.9). Likewise, the TPR response to hypoxemia was significantly blunted by lisinopril: 124 dyne·s·cm−5 vs placebo 179 dyne·s·cm−5 (95% CI, 11, 99). Lisinopril had no confounding systemic effects on mean arterial pressure, cardiac output, or systemic vascular resistance at baseline or in response to hypoxemia.

Conclusions

Lisinopril therefore significantly attenuated the pulmonary pressor response to hypoxemia without decreasing baseline MPAP or TPR. This suggests that angiotensin II might play a modulatory role during HPV in man and that ACE inhibition may be a useful adjunctive treatment in hypoxemic pulmonary hypertension.

Section snippets

Subjects

Ten healthy male volunteers, age (mean ± SEM) 27.2 ± 2.1 years (range, 20 to 37 years) were studied. Prior to inclusion, subjects were required to have no abnormality on clinical history or examination, and 12-lead ECG, echocardiogram, biochemical screening, and hematologic indexes were also normal. In addition, spot urinary sodium level was required to be more than 100 mmol/L and no medications were permitted during and for 1 month before the study. Informed written consent to the study

Pulmonary Hemodynamics

There was no significant difference in MPAP at baseline (ie, at T1) between the two study days: lisinopril, 9.2 ± 0.9 mm Hg, vs placebo, 8.6 ± 1.3 mm Hg (Fig 1, top). Likewise, TPR at T1 was similar on both study days: lisinopril, 121 ± 12 dyne·s·cm−5, vs placebo, 122 ± 22 dyne·s·cm−5 (Fig 1, bottom). Hypoxemia caused a significant (p<0.001) increase in MPAP on both study days, although MPAP at T2 was significantly (p<0.005) lower after lisinopril pretreatment (22.6± 1.0 mm Hg) compared with

DISCUSSION

In the present study, we have shown that acute HPV is significantly attenuated by lisinopril in normal humans. We believe this to be directly related to the suppressed plasma levels of ANG II rather than due to a nonspecific vasodilatory action.

It is also important to note that lisinopril pretreatment had no confounding effects on baseline pulmonary or systemic hemodynamic parameters prior to inducing hypoxemia. In the absence of an activated RAS, lisinopril, as would be expected, did not

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  • Cited by (0)

    This research program was supported by a grant from the Scottish Hospital Endowments Research Trust.

    revision accepted July 29.

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