Pulmonary vasodilation by acetazolamide during hypoxia: Impact of methyl-group substitutions and administration route in conscious, spontaneously breathing dogs

Pickerodt PA, Francis RCE, Hoehne C, Neubert F, Telalbasic S, Boemke W, Swenson ER (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Journal of Applied Physiology American Physiological Society

Book Volume: 116

Pages Range: 715-723

Journal Issue: 7

DOI: 10.1152/japplphysiol.01235.2013

Abstract

Acetazolamide (ACZ) prevents hypoxic pulmonary vasoconstriction (HPV) in isolated lungs, animals, and humans, but not by carbonic anhydrase (CA) inhibition. We studied administration routes in, and certain structural aspects of, ACZ critical to HPV inhibition. Analogs of ACZ during acute hypoxia were tested in unanesthetized dogs. Dogs breathed normoxic gas for 1 h (inspired O2 fraction = 0.21), followed by 10% O2 for 2 h (hypoxia) in these protocols: 1) controls; 2) ACZ intravenously (2 mg·kg^-1·h ^-1); 3) ACZ orally (5 mg/kg, 12 and 1 h before the experiment); 4) inhaled ACZ (750 mg); 5) methazolamide (MTZ) intravenously (3 mg·kg ^-1·h^-1); and 6) N-methyl-Acetazolamide (NMA) intravenously (10 mg·kg^-1·h^-1). In controls, mean pulmonary arterial pressure (MPAP) increased 7 mmHg, and pulmonary vascular resistance (PVR) 224 dyn·s·cm^-5 with hypoxia (P < 0.05). With intravenous and inhaled ACZ, MPAP and PVR did not change during hypoxia. With oral ACZ, HPV was only slightly suppressed; MPAP increased 5 mmHg and PVR by 178 dyn·s·cm^-5 during hypoxia. With MTZ and NMA, the MPAP rise (4 ± 2 mmHg) was reduced, and PVR did not increase during hypoxia compared with normoxia (MTZ intravenous: 81 ± 77 and 68 ± 82 dyn·s·cm^-5 with NMA intravenous). Inhaled ACZ prevents HPV, but not without causing systemic CA inhibition. NMA, a compound lacking CA inhibiting effects by methylation at the sulfonamide moiety, and MTZ, a CA-inhibiting analog methylated at the thiadiazole ring, are only slightly less effective than ACZ in reducing HPV. Copyright © 2014 the American Physiological Society.

Authors with CRIS profile

Roland Francis

Involved external institutions

Charité - Universitätsmedizin Berlin

Germany (DE) Universität Leipzig

Germany (DE) University of Washington

United States (USA) (US)

How to cite

APA:

Pickerodt, P.A., Francis, R.C.E., Hoehne, C., Neubert, F., Telalbasic, S., Boemke, W., & Swenson, E.R. (2014). Pulmonary vasodilation by acetazolamide during hypoxia: Impact of methyl-group substitutions and administration route in conscious, spontaneously breathing dogs. Journal of Applied Physiology, 116(7), 715-723. https://doi.org/10.1152/japplphysiol.01235.2013

MLA:

Pickerodt, Philipp A., et al. "Pulmonary vasodilation by acetazolamide during hypoxia: Impact of methyl-group substitutions and administration route in conscious, spontaneously breathing dogs." Journal of Applied Physiology 116.7 (2014): 715-723.

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