AZ, MZ, and the Pulmonary System Response to Hypoxia

The Effect of Carbonic Anhydrase Inhibitors on the Pulmonary System Response to Hypoxia

The purpose of this proposal is to compare the physiological effects of acetazolamide (AZ) and methazolamide (MZ) on the control of breathing and hypoxic pulmonary vasoconstriction. The first objective is to assess the effects of AZ and MZ on the control of breathing in normoxia and hypoxia. To achieve this the ventilatory interaction between oxygen and carbon dioxide will be measured and effects compared between placebo, AZ, and MZ conditions. In addition, the isocapnic and poikilocapnic hypoxic ventilatory response and hypercapnic ventilatory response will be measured with each drug. The second objective is to assess the effects of AZ and MZ on the control of the pulmonary vasculature during hypoxia. Pulmonary pressure and cardiac output will be measured during 60 minutes of poikilocapnic hypoxia.

Inclusion Criteria:

• 18-40 years of age
• regularly physically active
• male

Exclusion Criteria:

• ex-smokers
• pulmonary function <80% of predicted
• contraindications to carbonic anhydrase inhibitors (eg. severe or absolute glaucoma, adrenocortical insufficiency, hepatic insufficiency, renal insufficiency, sulfa allergy or an electrolyte imbalance such as hyperchloremic acidosis)
• Obese (BMI>30Kg/m2)
• diuretic medication use
• blood thinner use
• anti-platelet drug use.