Effects of moderate hypertension on cardiac function and metabolism in the rabbit.

Abstract

SUMMARY To study the early effects of hypertension on the heart, we examined isolated hearts from rabbits with slowly developing hypertension of up to 64 weeks in duration after unilateral nephrectomy and renal artery stenosis. Normotensive animals kept under identical conditions served as controls. Mean arterial blood pressure rose from 83 to 155 mm Hg in the hypertensive group of longest duration, but the ratio of left ventricular weight to body weight was not different between the experimental and control groups. Although left ventricular hypertrophy was not present, left ventricular peak systolic pressure of perfused hearts was significantly higher in hypertensive than in normotensive hearts. Furthermore, while in hypertensive hearts the left ventricular end-diastolic volume was increased, the peak systolic pressure did not respond to an increase in left ventricular enddiastolic volume. Functional changes were accompanied by metabolic changes in the left ventricle. Rates of glucose utilization were increased and rates of ketone body utilization were decreased hi hypertensive hearts. Activities of key enzymes of carbohydrate metabolism (phosphorylase, hexokinase, phosphofructokinase, and lactate dehydrogenase) were increased, while those of ketone body metabolism (3-oxoacid-CoA transferase, acetoacetyl-CoA synthase) were decreased and those of the citric acid cycle (citrate synthase, 2-oxoglutarate dehydrogenase) were not different between groups. In summary, moderate hypertension for a period of more than 1 year resulted in functional and metabolic changes of the left ventricle in hypertensive animals that were already manifest at 8 weeks of hypertension. The mechanism for the structural and functional adaptations that characterize the response of the left ventricle to hypertension may rest in changes of enzyme activities and resultant changes in substrate supply of the heart. (Hypertension 11: 416-426, 1988) KEY WORDS • renovascular hypertension activities * left ventricular function H YPERTENSION increases cardiac work by increasing plasma volume and peripheral vascular resistance. Sustained hypertension leads to changes in cardiac function and energy metabolism and, ultimately, to the development of cardiac hypertrophy. Adaptation of the heart to a high cardiac work load is important for survival of the organism as a whole and is governed by derepression of genetic information, leading to new synthesis of contractile proteins, mitochondria, and enzyme systems of myocardial energy production. Received February 17, 1987; accepted December 23, 1987. cardiac substrate metabolism • cardiac enzyme Acute pressure overload of the heart in experiments using banding of either the pulmonary artery or the aorta leads to rapid development of hypertrophy and a decrease in contractility in isolated papillary muscles, as measured by the rate of force development and the velocity of shortening by extrapolation to zero stress. 1More recent studies have reported decreased tensiondependent heat production and actin-act...

Carrier‐mediated transport controls hydroxyproline catabolism in heart mitochondria from spontaneously hypertensive rat

“…The carrier activity increase observed at the 24th week of life in spontaneously hypertensive rats is consistent with increased collagen concentration which requires an increase in catabolism [27,28]; thus, the increase in HYP transport rate may be assumed to be an adaptative response of the heart to an imposed work overload [29]. On the other hand, given that the sustained pressure load in spontaneously hypertensive rats is responsible for changes in cardiac function and energy metabolism and, ultimately, in the development of cardiac hypertrophy, adaptation of the heart to a high cardiac work load could lead both to changes in the activity of enzyme systems of myocardial energy production and to new synthesis of structural proteins [30][31][32][33][34], including the mitochondrial carriers. Thus, a change in Vm~, could be due to an increase in the number of carrier proteins (due to genetic alterations), however, a change in the membrane carrier environment, which might increase the specific carrier activity cannot be ruled out.…”

Glucose for the Heart

“…36,44 In both cases, the inciting stimulus of increased transport and oxidation seems to be an increase in Ca 2ϩ concentration. The increased heart work brought by systemic hypertension results in an enzymatic shift favoring the oxidation of glucose over fatty acids, 4 even in the absence of hypertrophy.…”

“…Since blood glucose concentration is maintained within a narrow range, glucose is a most reliable substrate for energy production in the heart. The importance of glucose metabolism via glycolysis is well appreciated in ischemic and hypertrophied heart muscle, [1][2][3][4] but aerobic glucose metabolism for support of normal contractile function has received less attention, mainly because of the well-known fact that fatty acids are normally the predominant fuel for cardiac energy production. 2,5,6 We have drawn attention to the heart as a true "omnivore," ie, an organ that functions best when it oxidizes different substrates simultaneously.…”

Myocardial substrate metabolism in obesity

“…21 The importance is again highlighted in the setting of heart failure and left ventricular (LV) hypertrophy, where mitochondrial oxidative capacity is reduced and metabolism shifts back towards a reliance on glucose metabolism, resembling the fetal metabolic program. 22,23 As the heart is an extremely efficient scavenger of circulating non-esterified FFAs (up to 40% extraction fraction), 24 the rate of fatty-acid uptake by the heart is primarily determined by the concentration of non-esterified fatty acids in the plasma. 25 The concentration of serum FFAs is highly regulated and represents a balance between production via hormone-sensitive lipaseinduced adipose tissue triglyceride breakdown and synthesis via glycerolphosphate acyltransferase.…”