title: Increased resistance to acute respiratory acidosis in isolated cardiac muscle following chronic hypoxia-induced hypertrophy.
abstract: OBJECTIVE
  Hypertrophied myocardium is more sensitive to ischaemic dysfunction and damage. The objective of this study was to determine the effect of respiratory acidosis on cardiac muscle function following hypoxia-induced right ventricular hypertrophy, and to ascertain the role of Na(+)-H+ antiporter, which is known to be associated with cell growth.
  
  
  METHODS
  Wistar rats were maintained at 10% O2 for 1 or 4 weeks. Experiments were performed on right ventricular papillary muscles stimulated at 1 Hz, and developed tension was recorded. The effect of respiratory acidosis was examined by equilibrating the perfusing solution with increasing levels of CO2, and the role of the Na(+)-H+ antiporter was determined by preincubation with the inhibitor 5-(N,N-hexamethylene) amiloride (HMA). Data were analysed by comparison of the slope of the semi-log plot of normalised tension against pH.
  
  
  RESULTS
  Right ventricular hypertrophy was apparent after both 1 and 4 weeks of hypoxia. Respiratory acidosis reduced developed force in preparations from all groups, but the relationship between log tension and pH in the 4-week hypoxia group was less steep than in controls (4-week hypoxia 0.736 (0.057); control 0.947 (0.067); P < 0.01). In the 1-week hypoxia group however the relationship was steeper (1.243 (0.090); P < 0.01). HMA increased the slope in all groups, and under these conditions the control and 4-week hypoxia groups were not significantly different (control 1.134 (0.080); 4-week hypoxic 1.083 (0.087); P > 0.05).
  
  
  CONCLUSIONS
  The increased resistance to respiratory acidosis of hypertrophied cardiac muscle following 4 weeks of hypoxia was abolished by HMA. This implies that it is related to increased activity of the Na(+)-H+ antiporter. The mechanism underlying the decreased resistance to acidosis following 1 week of hypoxia is unclear, but is unlikely to involve the Na(+)-H+ antiporter.
authors.affiliation: Department of Allergy and Respiratory Medicine, UMDS, London, UK.
authors.forename: E
authors.initials: E
authors.lastname: Neville
authors.forename: N T
authors.initials: NT
authors.lastname: Bateman
authors.forename: J P
authors.initials: JP
authors.lastname: Ward
mesh_terms: D000142:Acidosis, Respiratory / Q000378:metabolism*; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002908:Chronic Disease; D017380:Hypertrophy, Right Ventricular / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D010210:Papillary Muscles / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017923:Sodium-Hydrogen Exchangers / Q000187:drug effects / Q000502:physiology
chemical_list: D017923:Sodium-Hydrogen Exchangers; C057360:5-(N,N-hexamethylene)amiloride; D000584:Amiloride