Exercise intolerance in rats with hypertensive heart disease is associated with impaired diastolic relaxation.
A decrease in functional capacity is one of the most important clinical manifestations of hypertensive heart disease, but its cause is poorly understood. Our purpose was to evaluate potential causes of hypertension-induced exercise intolerance, focusing on identifying the type(s) of cardiac dysfunction associated with the first signs of exercise intolerance during the course of hypertensive heart disease. Exercise capacity was measured weekly in Dahl salt-sensitive rats as they developed hypertension as well as in Dahl salt-resistant control rats. Exercise capacity was unchanged from baseline during the first 8 weeks of hypertension, suggesting that hypertension itself did not cause exercise intolerance. After 9 to 12 weeks of hypertension, exercise capacity decreased in salt-sensitive rats but not in control rats. After 10 weeks of hypertension, indices of diastolic function (early truncation of the E wave), as assessed by echocardiography at rest, were decreased in the salt-sensitive rats. When exercise capacity had decreased by approximately 25% in a rat, the heart was isolated, and left ventricular (LV) compliance and systolic function were measured. At that time point, LV hypertrophy was modest (an approximately 20% increase in LV mass), and systolic function was normal or supernormal, indicating that exercise intolerance began during "compensated" LV hypertrophy. Passive LV compliance remained normal in salt-sensitive rats. Thus, in this model of hypertensive heart disease, exercise intolerance develops during the compensated stage of LV hypertrophy and appears to be due to changes in diastolic rather than systolic function. However, studies in which LV function is assessed during exercise are needed to conclusively define the roles of systolic and diastolic dysfunction in causing exercise intolerance.
Institute of Cardiology, University of Milan, Milan, Italy.
M
M
Guazzi
D A
DA
Brenner
C S
CS
Apstein
K W
KW
Saupe
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003971:Diastole / Q000187:drug effects / Q000502:physiology*; D004562:Electrocardiography; D017079:Exercise Tolerance / Q000502:physiology*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D020303:Rats, Inbred Dahl; D012982:Sodium, Dietary / Q000008:administration & dosage; D013599:Systole / Q000187:drug effects / Q000502:physiology; D016277:Ventricular Function, Left / Q000502:physiology
D012982:Sodium, Dietary