Tolerance to hypoxia of myocardium from adult and aged spontaneously hypertensive rats
Brooks, W.W.; Ingwall, J.S.; Conrad, C.H.; Holubarsch, C.; Bing, O.H.
American Journal of Physiology 252(6 Pt 2): H1096-H1104
1987
ISSN/ISBN: 0002-9513 PMID: 3591964 Document Number: 302866
Myocardial mechanics and high-energy phosphate content [ATP and creatine phosphate (CrP)] of isolated left ventricular papillary muscle preparations from male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were compared at 6 and 18 mo of age. In comparison with oxygenated (95% O2-5% CO2) glucose-supplied (5.5 mM) papillary muscles from hearts of WKY rats, papillary muscles from hypertrophied hearts of the 18-mo-old SHR exhibited a prolonged time to peak tension, electromechanical delay time, and an increase in resting tension measured at the apex of the length-tension curve. Adenine nucleotide (ATP and ADP) contents of oxygenated papillary muscles were not significantly different between SHR and WKY strains at 6 or 18 mo of age, but CrP content of hearts from adult WKY and SHR were higher than for aged WKY and SHR rats. For up to 30 min of hypoxia (95% N2-5% CO2), muscles from the 18-mo-old SHR and WKY rats demonstrated improved tolerance to hypoxia compared with muscles from younger animals. However, at 60 min of hypoxia the 18-mo-old SHR demonstrated lower active tension and adenylate energy charge [(1/2 ADP + ATP)/(ATP + ADP + AMP)]. At higher glucose concentrations (22 mM), both 18-mo-old WKY and SHR demonstrated improved tolerance to hypoxia; moreover, the differences between strains were no longer evident. Following reoxygenation with 5.5 mM glucose, contracture tension and CrP content recovered to near prehypoxic control levels, whereas developed tension and ATP content remained moderately depressed for all groups. Thus papillary muscles from both the 18-mo-old SHR and WKY show an age-related increase in tolerance to early hypoxia (30 min); with prolonged hypoxia (60 min) in the presence of limited exogenous glucose (5.5 mM), hypertrophied preparations from the 18-mo-old SHR had the lowest adenylate energy charge and did not sustain this tolerance.