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The acetazolamide analogue N‐methyl acetazolamide does not alter the ventilatory response to hypoxia but reduces the hypercapnic response in the anesthetized cat
Author(s) -
Teppema Luc J,
Dahan Albert,
Swenson Erik R
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.799.29
Subject(s) - acetazolamide , hypercapnia , chemistry , cats , hypoxia (environmental) , hypoxic ventilatory response , hyperoxia , carbonic anhydrase , anesthesia , respiratory system , ventilation (architecture) , endocrinology , medicine , oxygen , biochemistry , mechanical engineering , organic chemistry , engineering , enzyme
Acetazolamide (AZ) may have cardiorespiratory effects independently from inhibition of carbonic anhydrase (CA). In contrast to methazolamide, it impairs respiratory muscle function in rabbits and reduces the hypoxic ventilatory response in cats. In rat pulmonary arterial smooth muscle cells, AZ inhibits the hypoxia‐induced rise in [Ca 2+ ] i , an effect that is shared by N‐methyl acetazolamide (NMA), an AZ analogue devoid of inhibiting effects on CA. We have studied the effect of NMA on the ventilatory response to hypoxia and hypercapnia in 7 anesthetized cats. NMA, (20 mg.kg −1 , i.v.) did not influence the hypoxic response measured at a constant end‐tidal PCO 2 of about 6 kPa, described with the exponential equation V i (inspired ventilation) = G.{(exp) − DPO 2 } + R, with G = hypoxic sensitivity, D = shape factor and R = ventilation in hyperoxia. Mean values of G, D and R were not different in control and following NMA. Surprisingly however, the ventilatory CO 2 response curve described with V i = S(PCO 2 −B) with the CO 2 sensitivity S and the extrapolated X‐intercept (apneic threshold) B underwent dramatic changes: S and B decreased by 60 and 72%, respectively. Whether these effects of NMA may be due to vascular effects remains to be examined.