Increased resistance to acute respiratory acidosis in isolated cardiac muscle following chronic hypoxia-induced hypertrophy.
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.
Neville
E
E
Department of Allergy and Respiratory Medicine, UMDS, London, UK.
Bateman
N T
NT
Ward
J P
JP
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
D017923:Sodium-Hydrogen Exchangers; C057360:5-(N,N-hexamethylene)amiloride; D000584:Amiloride