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(Hypertension. 1997;29:15.)
© 1997 American Heart Association, Inc.

Research Articles (Issue 1, Part 1)

Senescent Heart Compared With Pressure Overload–Induced Hypertrophy

Patrick Assayag; Danièle Charlemagne; Joël de Leiris; François Boucher; Paul-Etienne Valère; Sylviane Lortet; Bernard Swynghedauw; Sophie Besse

the Institut National de la Santé et de la Recherche Médicale (INSERM) U127, IFR Circulation, Hôpital Lariboisière, Paris (P.A., D.C., B.S.); Service de Cardiologie, Hôpital Bichat-Claude Bernard, Paris (P.A., P.-E.V.); Faculté de Pharmacie Université Aix-Marseille II, Marseille (S.L.); and Laboratoire de Physiopathologie Cellulaire Cardiaque, ESA CNRS 5077 (J. de L., F.B., S.B.), Université Joseph Fourier, Grenoble, France.

Correspondence to Dr Sophie Besse, Laboratoire de Physiopathologie Cellulaire Cardiaque, ESA CNRS 5077, 2280 rue de la Piscine, Université Joseph Fourier, BP 53X, 38041 Grenoble Cedex, France.

Although systolic left ventricular (LV) function is normal in the elderly, aging is associated in rat papillary muscle with mechanical and sarcoplasmic reticulum Ca²⁺ ATPase alterations similar to those observed in the hypertrophied heart. However, alterations in the other calcium-regulating proteins implicated in contraction and relaxation are still unknown. To investigate alterations in LV function and calcium-regulating proteins, we measured hemodynamics and Na⁺-Ca²⁺ exchanger (NCx), ryanodine receptor (RyR2), and sarcoplasmic reticular Ca²⁺ ATPase (SERCA2) mRNA levels (expressed in densitometric scores normalized to that of poly(A⁺) mRNA) in left ventricle from 4-month-old (adult, n=13) and 24-month-old (senescent, n=15) rats. For ex vivo contractile function, active tension was measured during isolated heart perfusion in adult (n=11) and senescent (n=11) rats. For comparison of age-dependent effects of moderate hypertension on both hemodynamics and calcium proteins, renovascular hypertension was induced or a sham operation performed at 2 (n=11 and n=6) and 22 (n=26 and n=5) months of age. In senescent rats, LV systolic pressure and maximal rates of pressure development were unaltered, although active tension was depressed (4.7±0.4 versus 8.3±0.7 g/g heart weight in adults, P<.0001). SERCA2 mRNA levels were decreased in senescent left ventricle (0.98±0.05 versus 1.18±0.05 in adults, P<.01), without changes in NCx and RyR2 mRNA accumulation. Renovascular hypertension resulted in 100% mortality in aged rats; in adults, renovascular hypertension resulted, 2 months later, in an increase of LV systolic pressure (170±7 versus 145±3 mm Hg in sham-operated rats, P<.05) and in mild LV hypertrophy (+18%, P<.01) associated with a decrease in SERCA2 mRNA levels (1.02±0.03 versus 1.18±0.03 in sham-operated rats, P<.001). Contractile dysfunction in senescent isolated heart and decreased SERCA2 mRNA levels were associated with in vivo normal LV function at rest, indicating the existence of in vivo compensatory mechanisms. RyR2 and NCx gene expressions were not implicated in the observed contractile dysfunction. In aged rats, renovascular hypertension resulted in 100% mortality, probably related to elevated levels of circulating angiotensin II, whereas in adult rats, renovascular hypertension induced a mild LV hypertrophy associated with a selective alteration in SERCA2 gene expression.

Key Words: aging • antiporters, sodium-calcium • Ca²⁺-transporting ATPase • ryanodine • hemodynamics • heart

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