Time course of regression of the protection conferred by simulated high altitude to rat myocardium: correlation with mtNOS.
During acclimatization to sustained hypobaric hypoxia, retardation of age-associated decline in left ventricle mechanical activity and improved posthypoxic recovery were accompanied by upregulation of mitochondrial nitric oxide synthase (mtNOS). To evaluate the time course of regression of these effects on deacclimatization, rats exposed to 53.8 kPa in a hypopressure chamber for 5 mo were returned to 101.3 kPa, whereas controls remained at 101.3 kPa throughout the study. At three time points, contractile function in response to calcium and to hypoxia-reoxygenation (H/R) were determined in papillary muscle, and NOS activity and expression were determined in mitochondria isolated from left ventricle. Developed tension was, before H/R, 65, 58, and 40%, and, after H/R, 129, 107, and 71% higher than in controls at 0.4, 2, and 5 mo of normoxia, respectively. Maximal rates of contraction and relaxation followed a similar pattern. All three parameters showed a linear decline during deacclimatization, with mean half-time (t(1/2)) of 5.9 mo for basal mechanical activity and 5.3 mo for posthypoxic recovery. Left ventricle mtNOS activity was 42, 27, and 20% higher than in controls at 0.4, 2, and 5 mo, respectively (t(1/2) = 5.0 mo). The expression of mtNOS showed similar behavior. The correlation of mtNOS activity with muscle contractility sustained a biphasic modulation, suggesting an optimal mtNOS activity. This experimental model would provide the most persistent effect known at present on preservation of myocardial mechanical activity and improved tolerance to O(2) deprivation. Results support the putative role of mtNOS in the mechanism involved.
Instituto de Investigaciones Cardiológicas, Marcelo T. de Alvear 2270, C1122AAJ Buenos Aires, Argentina.
Pablo
P
La Padula
Juanita
J
Bustamante
Analía
A
Czerniczyniec
Lidia E
LE
Costa
D000064:Acclimatization; D000375:Aging / Q000378:metabolism; D000531:Altitude; D000818:Animals; D001274:Atmospheric Pressure; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D004790:Enzyme Induction; D000860:Hypoxia / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology*; D009200:Myocardial Contraction; D009206:Myocardium / Q000201:enzymology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D010210:Papillary Muscles / Q000201:enzymology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D016277:Ventricular Function, Left
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D002118:Calcium