Morphometry of the renal corpuscle during normal postnatal growth and compensatory hypertrophy. A light microscope study.

Renal corpuscles from the juxtamedullary and subcapsular regions of the renal cortex were morphometrically analyzed in young rats and in adult rats that had been unilaterally nephrectomized or sham-operated at an early age. Mean corpuscular volumes increased 4.5-fold during normal development, and 7.7-fold as a result of compensatory hypertrophy in both cortical regions. Relative and absolute volumes were determined for Bowman's space, the glomerular tuft, and five glomerular components: epithelial, endothelial, and mesangial cells, capillaries, and the filtration membrane. Normal and hypertrophic enlargement of Bowman's space was slightly greater than glomerular growth, and the growth response of subcapsular glomeruli was greater than that of juxtamedullary glomeruli. The ratio of mean glomerular volumes between outer and inner glomeruli was 1:2 in both adult groups. Both adult groups also developed nearly identical proportions of all glomerular component structures, representing a relative decrease of epithelial cells and increase of capillaries compared to the young animals. Normal and hypertrophic maturation involved absolute increases in all glomerular cell populations, the length of capillary loops and the surface area of the filtration membrane, all nearly in proportion to the respective four- and seven-fold increases in glomerular volume. Changes in the filtration surface area are consistent with published data for glomerular filtration rates in normal and hypertrophied kidneys. The mean cell size in epithelial and mesangial populations doubled during growth, but was not greater than normal in mononephrectomized rats. Hyperplasia among all populations of glomerular cells is indicated in normal growth, and to a greater extent in compensatory renal hypertrophy.

Hyperplasia of myocyte nuclei in long-term cardiac hypertrophy in rats.

In contrast to observations made in the human heart, hyperplasia of myocyte nuclei has never been demonstrated in experimental cardiac hypertrophy. To test the hypothesis that the duration of the mechanical load more than the magnitude of ventricular hypertrophy may be the inciting stimulus for myocyte nuclei hyperplasia, constriction of the pulmonary artery was produced in rats and the hearts were examined 6 mo later. A 76% increase in right ventricular weight was measured. This hypertrophic response was accompanied by a 41% increase in the total number of myocyte nuclei in the ventricle. Furthermore, average myocyte cell volume per nucleus increased by 28%. No changes in weight, myocyte size, and nuclear number were observed in the left ventricle. In conclusion, myocyte nuclear hyperplasia and cellular hypertrophy both participate to the adaptive response of the right ventricular myocardium in long-standing pressure overload cardiac hypertrophy.

Hypertensive cardiomyopathy. Myocyte nuclei hyperplasia in the mammalian rat heart.

To determine whether long-term hypertension leads to hyperplasia of myocyte nuclei in the heart, a phenomenon suspected to occur in humans, renal hypertension was produced in rats and the animals were killed 8 mo later. Arterial blood pressure remained elevated for approximately 5 mo, but decreased progressively in the last 3 mo so that at 8 mo this parameter was practically identical to that found in controls. Moreover, left ventricular end diastolic pressure was markedly increased in experimental animals in association with a substantial decrease in left ventricular dP/dt. The alteration of these physiological measurements was indicative of severe ventricular dysfunction. Quantitative analysis of the transmural distribution of myocyte nuclei in the left ventricle showed 36 and 23% increases in myocyte nuclei concentration in the epimyocardium and endomyocardium, respectively. These changes in nuclei were accompanied by 25 and 16% reductions in myocyte cell volume per nucleus in the outer and inner layers of the wall. In conclusion, long-term hypertension leads to impairment of ventricular function and proliferation of nuclei in myocytes.

Stretch-induced programmed myocyte cell death.

To determine the effects of loading on active and passive tensions, programmed cell death, superoxide anion formation, the expression of Fas on myocytes, and side-to-side slippage of myocytes, papillary muscles were exposed to 7-8 and 50 mN/mm2 and these parameters were measured over a 3-h period. Overstretching produced a 21- and a 2.4-fold increase in apoptotic myocyte and nonmyocyte cell death, respectively. Concurrently, the generation of reactive oxygen species increased 2.4-fold and the number of myocytes labeled by Fas protein 21-fold. Moreover, a 15% decrease in the number of myocytes included in the thickness of the papillary muscle was found in combination with a 7% decrease in sarcomere length and the inability of muscles to maintain stable levels of passive and active tensions. The addition of the NO-releasing drug, C87-3754, prevented superoxide anion formation, programmed cell death, and the alterations in active and passive tensions with time of overloaded papillary muscles. In conclusion, overstretching appears to be coupled with oxidant stress, expression of Fas, programmed cell death, architectural rearrangement of myocytes, and impairment in force development of the myocardium.

PTX3, A prototypical long pentraxin, is an early indicator of acute myocardial infarction in humans.

BACKGROUND: Inflammation is an important component of ischemic heart disease. PTX3 is a long pentraxin whose expression is induced by cytokines in endothelial cells, mononuclear phagocytes, and myocardium. The possibility that PTX3 is altered in patients with acute myocardial infarction (AMI) has not yet been tested. METHODS AND RESULTS: Blood samples were collected from 37 patients admitted to the coronary care unit (CCU) with symptoms of AMI. PTX3 plasma concentrations, as measured by ELISA, higher than the mean+2 SD of age-matched controls (2.01 ng/mL) were found in 27 patients within the first 24 hours of CCU admission. PTX3 peaked at 7.5 hours after CCU admission, and mean peak concentration was 6.94+/-11.26 ng/mL. Plasma concentrations of PTX3 returned to normal in all but 3 patients at hospital discharge and were unrelated to AMI site or extent, Killip class at entry, hours from symptom onset, and thrombolysis. C-reactive protein peaked in plasma at 24 hours after CCU admission, much later than PTX3 (P<0.001). Patients >64 years old and women had significantly higher PTX3 concentrations at 24 hours (P<0.05). PTX3 was detected by immunohistochemistry in normal but not in necrotic myocytes. CONCLUSIONS: PTX3 is present in the intact myocardium, increases in the blood of patients with AMI, and disappears from damaged myocytes. We suggest that PTX3 is an early indicator of myocyte irreversible injury in ischemic cardiomyopathy.

Quantitative structural analysis of the myocardium during physiologic growth and induced cardiac hypertrophy: a review.

The quantitative structural properties of the ventricular myocardium during postnatal physiologic growth are compared with those accompanying an increased load in the adult rat heart to determine whether induced cardiac hypertrophy is a pathologic condition or simply a form of well compensated accelerated growth. The expansion of the ventricular myocardium during maturation shows a remarkable degree of well balanced compensatory response, because the capillary microvasculature, parenchymal cells and subcellular components of myocytes all grow in proportion to the increase in cardiac mass. In contrast, the increases in myocyte diameter and length caused by pressure hypertrophy, volume hypertrophy and infarction-induced hypertrophy are consistent with concentric, eccentric and a combination of concentric and eccentric hypertrophic growth of the whole ventricle, respectively. These cellular shape changes may represent a compensatory response of the myocardium at the cellular level of organization that tends to minimize the effects of an increased pressure or volume load, or both, on the heart. Cardiac hypertrophy, however, may also show alterations affecting capillary luminal volume and surface and the mitochondrial to myofibril volume ratio, which indicate an inadequate growth adaptation of the component structures responsible for tissue oxygenation and energy production. Thus, hypertrophy of the adult heart differs from that during physiologic growth, and the hypertrophied myocardium may exhibit structural abnormalities that can be expected to increase its vulnerability to ischemia.

Myocyte cell loss and myocyte hypertrophy in the aging rat heart.

To determine the effects of age on the myocardium, the functional and structural characteristics of the heart were studied in rats at 3, 10 to 12 and 19 to 21 months of age. Systemic arterial pressure, left ventricular pressure and its first derivative (dP/dt) and heart rate were comparable in the three animal groups. In the interval between 3 and 10 to 12 months, mean myocyte cell volume per nucleus increased 53 and 26% in the left and the right ventricle, respectively. The total number of myocyte nuclei remained constant in either ventricle. In the following period, between 10 to 12 and 19 to 21 months, a 39% further cellular hypertrophy on the left side of the heart was found in association with an 18% loss of cells in the ventricle. Cell loss was accompanied by discrete areas of interstitial and replacement fibrosis in the subendocardium. In contrast, no myocardial damage was observed in the right ventricle, and the measured 35% additional enlargement of myocytes occurred without a change in cell number. Thus, the aging left ventricle is composed of a smaller number of hypertrophied cells. Cellular hypertrophy may explain the unaltered cardiac function of the aged myocardium.

Myocyte nuclear and possible cellular hyperplasia contribute to ventricular remodeling in the hypertrophic senescent heart in humans.

OBJECTIVES: The present investigation was designed to evaluate the growth reserve capacity of the aged and senescent myocardium. BACKGROUND: Aging affects the ability of the heart to sustain alterations in ventricular loading, and this phenomenon may be coupled with attenuation of the hypertrophic reaction of the myocardium. However, because myocyte cellular hyperplasia has been documented experimentally in the old heart, a similar adaptation may also occur in humans and play a role in this process. METHODS: The changes in number and size of ventricular myocytes were measured quantitatively in pathologic hearts of elderly subjects. Morphometric methodologies were applied to the analysis of 13 hypertrophic hearts obtained at autopsy from patients 80 +/- 4 (mean +/- SD) years old. An identical number of nonhypertrophic hearts collected from subjects 76 +/- 7 years old were used as control hearts. RESULTS: A 71% increase in left ventricular weight was associated with a 33% increase in average myocyte cell volume per nucleus and a 36% augmentation in the total number of myocyte nuclei in the ventricular myocardium. However, a 55% increase in right ventricular weight was the result of a 59% increase in the aggregate number of myocyte nuclei, with no change in myocyte cell volume. These cellular processes were associated with a 95% and 83% enlargement of the myocardial interstitium in the left and right ventricle, respectively. CONCLUSIONS: Myocyte nuclear and possibly cellular hyperplasia appear to be the prevailing growth mechanism of the overloaded aging myocardium. Proliferation of myocyte nuclei and connective tissue accumulation are the major determinants of ventricular remodeling in the hypertrophic senescent heart.

Gender differences and aging: effects on the human heart.

OBJECTIVES: This study investigated the changes in myocyte size and number in the left and right ventricles that occur with aging in the female and male heart. BACKGROUND: Differences in life span between women and men may be related to a better preservation of myocardial structure in the female heart with aging. On this basis, the hypothesis was advanced that the aging process has a different impact on the integrity of the myocardium in the two genders. METHODS: Morphometric methodologies were applied to analyze the changes in number and size of ventricular myocytes in the hearts of 53 women and 53 men. The changes in mononucleated and binucleated myocytes with age were determined in enzymatically dissociated cells. The age interval examined varied from 17 to 95 years. RESULTS: Aging was associated with a preservation of ventricular myocardial mass, aggregate number of mononucleated and binucleated myocytes, average cell diameter and volume in the female heart. In contrast, nearly 1 g/year of myocardium was lost in the male heart, and this phenomenon accounted for the loss of approximately 64 million cells. This detrimental effect involved the left and right sides of the heart. In the remaining cells, myocyte cell volume increased at a rate of 158 microns3/year in the left and 167 microns3/year in the right ventricle. CONCLUSIONS: Aging does not lead to myocyte cell loss and myocyte cellular reactive hypertrophy in women, indicating that gender differences may play a significant role in the detrimental effects of the aging process on the heart.

Unusual immunologic findings in familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an inherited disease of unknown etiology. We report a case in which, during an acute febrile attack, rheumatoid factor and immunoglobulin levels rose, and the levels of complement components fell. The level of urinary fibrinogen degradation products also increased, and all results of tests returned to normal at the end of the acute attack. This suggests that an immunologic phenomenon may play a substantial role in the etiology of FMF.

Effects of genetic hypertension and nutritional anaemia on ventricular remodelling and myocardial damage in rats.

OBJECTIVE: In order to determine whether alterations in cardiac function and structure occur early in life in spontaneously hypertensive rats (SHR) and whether the addition of a volume load would affect myocardial growth and haemodynamic performance, SHR were exposed to an iron and copper deficient diet for 12 weeks (SHR-A) and compared with untreated SHR and Wistar Kyoto controls (WKY). RESULTS: Systolic arterial blood pressure increased in SHR, whereas nutritional anaemia prevented the rise of blood pressure in SHR-A. The diet employed provoked a severe hypochromic microcytic anaemia with a marked reduction in blood viscosity and increased volume load on the heart in SHR-A. Genetically determined hypertension alone induced a 16% increase in left ventricular weight and an increase in left ventricular peak systolic pressure (LVPSP) and +dP/dt. The superimposition of anaemia resulted in a 43% expansion in left ventricular weight with a decrease in LVPSP and +dP/dt, and an increase in left ventricular end diastolic pressure. Wall thickening and a preservation of chamber volume occurred in SHR, while SHR-A had a degree of ventricular dilatation which exceeded the extent of wall thickening. However, genetic hypertension was accompanied by myocardial tissue injury which was fully prevented by the addition of nutritional anaemia. Moreover, the capillary volume was decreased in SHR and increased in SHR-A. CONCLUSIONS: Genetically determined hypertension in combination with anaemia results in eccentric ventricular hypertrophy and cardiac dysfunction in spite of an increase in capillary luminal volume and limited structural damage.

Myocyte cellular hypertrophy is responsible for ventricular remodelling in the hypertrophied heart of middle aged individuals in the absence of cardiac failure.

OBJECTIVE: The aim was to measure changes in the numbers and size of ventricular myocytes in human hearts with marked ventricular hypertrophy and no clear signs of cardiac failure, to determine whether myocyte cellular hypertrophy is the only factor involved in the increase in cardiac mass. METHODS: Morphometric techniques were applied to estimate the number of myocyte nuclei per unit volume of myocardium which, in combination with the determination of the volume percent of myocytes, allowed the computation of the average myocyte cell volume per nucleus and total number of myocyte nuclei in the ventricles. Subsequently, the volume fraction of replacement fibrosis in the tissue was assessed and absolute component volumes in the ventricles obtained. RESULTS: Eight hypertrophied human hearts, weight 561(SD 68) g, were collected at necropsy from hypertensive patients who died from non-cardiac causes and were compared with eight normal hearts, weight 387(37) g, obtained from healthy individuals who also died from non-cardiac causes. With cardiac hypertrophy, left and right ventricular weight increased by 53% and 57%, whereas myocyte cell volume increased by 112% and 84%, respectively. The disproportion between the increase in ventricular weight and the increase in myocyte volume was due to a 30% and 16% loss in left and right ventricular myocytes following hypertensive hypertrophy. Myocyte loss also provoked a 319% and a 188% increase in the amount of replacement fibrosis in the left and right ventricular myocardium. These tissue and cellular processes resulted in an expansion in ventricular mass which exceeded the thickening of the wall so that an increase in cavitary volume occurred in both ventricles. CONCLUSIONS: Myocyte cellular hypertrophy is responsible for ventricular hypertrophy in hypertensive cardiomyopathy in its compensated stage. Myocyte loss precedes the impairment in ventricular pump function and may be implicated in the initiation of ventricular maladaptation.

Dependence of temporal variability of ventricular recovery on myocardial fibrosis. Role of mechanoelectric feedback?

OBJECTIVE: The study was aimed at establishing the effect of factors involved in the expression of mechanoelectric feedback in the heart, such as R-R interval and connective tissue, on time dependent changes in ventricular recovery, as determined at the body surface by beat to beat variability of QRST integral maps (BBV-IM). METHODS: We used 15 normal 6-month-old Wistar rats. In each anesthetized animal, we performed a 3-minute continuous recording of 44. The simultaneous chest ECGs. The signals were interactively processed, 1) to determine mean R-R interval and R-R variability throughout the recording period and 2) to compute QRST integral maps from approximately 50 beats belonging to the end of expiration. Then BBV-IM was calculated and expressed as percentage of beats significantly differing from a template. At sacrifice, the amount of myocardial fibrosis was morphometrically evaluated. RESULTS: R-R interval was 149 ms +/- 4, R-R interval variability 0.008 +/- 0.001 and BBV-IM 30.7% +/- 4.4. Myocardial fibrosis expressed as % volume of left ventricular myocardium, numerical density of fibrotic foci and average cross-sectional area of the foci was 3.0% +/- 0.4, 3.8 +/- 0.6 and 4.4 microns(2)/1000 +/- 0.1 respectively, BB-IM was positively correlated to the % volume of fibrosis (r = 0.83, P < 0.0003). Both measurements were positively correlated to R-R interval (BBV-IM: r = 0.83, P < 0.0001; % volume of fibrosis: r = 0.87, P < 0.001) and negatively correlated to cardiac weights (BBV-IM: r = -0.79, P < 0.0005; % volume of fibrosis: r = -0.75, P < 0.001). CONCLUSION: Beat to beat changes in ventricular repolarization attributable to mechanoelectric transduction can be detected at the body surface by means of BBV-IM.

Connective tissue accumulation in the left coronary artery of young SHR.

The left coronary artery of 21-, 28-, and 45-day-old spontaneously hypertensive rats and Wistar-Kyoto rats was analyzed morphometrically to evaluate the structural alterations of the vessel wall during the development of genetically determined hypertension. In 45-day-old rats, hypertension was associated with a significant expansion of the partial volume of collagen and ground substance (119%) within the arterial wall. This change exceeded the concurrent accumulation of elastin (77%) and smooth muscle cell mass (34%). The growth of the muscle compartment was also characterized by a marked increment of rough endoplasmic reticulum (103%). The increase in the mural concentration of fibrous proteins at this early age may be viewed as the initial adverse effect of hypertension on muscular arteries.

Angiotensin II type 1 receptor blockade prevents cardiac remodeling in bradykinin B(2) receptor knockout mice.

Knockout mice (B(2)(-/-)) lacking the bradykinin (BK) B(2) receptor gene develop mild hypertension, cardiac hypertrophy, and myocardial damage. We hypothesized that these effects are due to the hypertrophying and damaging actions of angiotensin II (Ang II) in the absence of the balancing protection of BK. To verify this hypothesis, B(2)(-/-) or wild-type mice (B(2)(+/+)) were administered a nonpeptide antagonist of Ang II type 1 (AT(1)) receptors (A81988) from conception through 180 days of age. Untreated B(2)(+/+) and B(2)(-/-) served as controls. Blood pressure (BP) and heart rate were monitored with the use of tail-cuff plethysmography at regular intervals. Ventricular weights, diameters, wall thickness, chamber volume, and myocardial fibrosis were measured at 40 and 180 days. No differences were observed in BP, heart rate, and cardiac weight and dimensions between treated and untreated B(2)(+/+). The BP of AT(1) antagonist-treated B(2)(-/-) was reduced until 70 days; then, it increased to the levels found in untreated B(2)(-/-). AT(1) receptor blockade resulted in a reduction in left ventricular mass, chamber volume, and wall thickness and abrogated myocardial fibrosis in B(2)(-/-). These results indicate that Ang II is the major factor responsible for ventricular remodeling and myocardial damage in mice with disruption of BK B(2) receptor signaling. The interaction of Ang II and BK appears to be essential for the development of a normal heart.

Enalapril prevents cardiac fibrosis and arrhythmias in hypertensive rats.

To evaluate the effects of hypertension on cardiac hypertrophy, on myocardial structure, and on ventricular arrhythmias, 27 3-month-old spontaneously hypertensive rats were treated with enalapril (10 mg/kg) daily for 11 months and compared with 26 untreated control rats. Systolic arterial pressure was significantly decreased in treated rats, and at the end of the experiment, it was 199 +/- 3 mm Hg (treated) versus 237 +/- 3 mm Hg (controls) (p less than 0.001). At this time, spontaneous arrhythmias and induced arrhythmias either by programmed electrical stimulation (train of stimuli +1 or 2 extrastimuli) or by trains of eight stimuli at decreasing coupling intervals were observed in isolated heart preparations. Comparing enalapril-treated and control rats, spontaneous arrhythmias (9 of 27 versus 20 of 26, respectively; p less than 0.01), programmed stimulation-induced arrhythmias (3 of 26 versus 12 of 23, respectively; p less than 0.01), and trains of stimuli-induced arrhythmias (4 of 26 versus 14 of 19, respectively, p less than 0.001) were less frequent in the enalapril group. Left ventricular weight was decreased in treated rats by 18% (p less than 0.001). Enalapril administration diminished the fraction of myocardium occupied by foci of replacement fibrosis normally occurring in control rats by 59% (p less than 0.001). Finally, a significant correlation was found between left ventricular weight, the extent of myocardial fibrosis, and the occurrence of ventricular fibrillation. It was concluded that chronic treatment with enalapril, which resulted in attenuation of systemic arterial pressure by limiting cardiac hypertrophy and myocardial fibrosis, decreases the propensity of the heart of hypertensive rats to arrhythmogenesis.

Cellular basis of ventricular remodeling after myocardial infarction.

To determine whether acute left ventricular failure associated with myocardial infarction leads to architectural changes in the spared nonischemic portion of the ventricular wall, large infarcts were produced in rats, and the animals were sacrificed 2 days after surgery. Left ventricular end-diastolic pressure was increased, whereas left ventricular dP/dt and systolic pressure were decreased, indicating the presence of severe ventricular dysfunction. Absolute infarct size, determined by measuring the fraction of myocyte nuclei lost from the left ventricular free wall, averaged 63%. Transverse midchamber diameter increased by 20%, and wall thickness diminished by 33%. The number of mural myocytes in this spared region of the left ventricular free wall decreased by 36% and the capillary profiles by 40%. Thus, side-to-side slippage of myocytes in the myocardium occurs acutely in association with ventricular dilation after a large myocardial infarction. In order to analyze the chronic consequences of myocardial infarction on ventricular remodeling, a second group of experiments was performed in which the left coronary artery was ligated and the functional and structural properties of the heart were examined 1 month later. In infarcts affecting an average 38% of the free wall of the left ventricle (small infarcts), reactive hypertrophy in the spared myocardium resulted in a complete reconstitution of functioning tissue. However, left ventricular end-diastolic pressure was increased, left ventricular dP/dt was decreased, and diastolic wall stress was increased 2.4-fold. After infarctions resulting in a 60% loss of mass (large infarcts), a 10% deficit was present in the recovery of viable myocardium. Functionally, ventricular performance was markedly depressed, and diastolic wall stress was increased 9-fold. The alterations in loading of the spared myocardium were due to an increase in chamber volume and a decrease in the myocardial mass/chamber volume ratio that affected both infarct groups. Thus, decompensated eccentric ventricular hypertrophy develops chronically after infarction and growth processes in myocytes are inadequate for normalization of wall stress when myocyte loss involves nearly 40% or more of the cells of the left ventricular free wall. The persistence of elevated myocardial and cellular loads may sustain the progression of the disease state toward end-stage congestive heart failure.

Coronary artery constriction in rats: necrotic and apoptotic myocyte death.

The purpose of this study was to determine whether coronary artery narrowing was associated with the activation of necrotic and apoptotic myocyte cell death in the myocardium and whether these 2 forms of cell death were restricted to the left ventricle, or involved the other portions of the heart. Coronary artery narrowing was surgically induced in rats, and the animals were killed from 45 minutes to 12 days after surgery. Myocyte apoptosis was detected by the terminal deoxynucleotidyl transferase assay, confocal microscopy, and deoxyribonucleic acid (DNA) agarose gel electrophoresis. Myocyte necrosis was identified by myosin monoclonal antibody labeling of the cytoplasm. A separate group of animals was treated with trimetazidine in an attempt to interfere with tissue injury. Coronary artery narrowing was characterized by myocyte apoptosis in the left ventricle and interventricular septum, which progressively increased from 45 minutes to 6 days. However, apoptosis was not observed at 12 days. Conversely, myocyte necrosis reached its maximum value at 1 day and was still present at 12 days. This form of cell death affected not only the left ventricular free wall and interventricular septum, but also the right ventricle. Cell necrosis markedly exceeded apoptosis at all intervals. At the peak of cell death, myocyte necrosis was 52-fold and 33-fold higher than apoptosis in the left ventricle and septum. In conclusion, necrotic myocyte cell death is the prevailing form of damage produced by coronary artery narrowing, but apoptotic cell death contributes to the loss of myocytes in the ischemic heart. Trimetazidine treatment attenuated the extent of myocardial damage produced by global ischemia.

Cellular basis of ventricular remodeling in hypertensive cardiomyopathy.

This review summarizes the effects of long-term pressure overload hypertrophy on the right and left ventricular myocardium. In particular, the role that the fundamental processes of myocyte growth plays in the remodeling of the wall is analyzed quantitatively. Moreover, emphasis is placed on the observation that the duration of the overload is an important component of the onset, development, and progression of time-dependent myocardial dysfunction associated with hypertensive cardiomyopathy. The deterioration in ventricular pump function is postulated to be accompanied by myocyte cellular hyperplasia and capillary proliferation in an attempt to increase the thickness of the ventricular wall and, consequently, to decrease the magnitude of systolic and diastolic stress generated by the elevation in ventricular systolic and end-diastolic pressures. Myocyte cellular hyperplasia constitutes an essential growth reserve mechanism of the heart. Regeneration of damaged and lost myocardium may be accomplished by hyperplasia of myocytes, a phenomenon considered not feasible for several decades.

Comparison of the metabolic changes in rats with hypertension secondary to fructose feeding or renal artery stenosis.

Hypertension was induced in rats by either renal artery stenosis or a fructose-enriched diet, and the consequent changes in plasma glucose, insulin, and triglyceride (TG) concentrations, and the steady-state plasma insulin (SSPI) and glucose (SSPG) concentrations in response to a 180-min continuous infusion of glucose and insulin in these two groups of hypertensive rats, were compared to values in a sham-operated group with normal blood pressure. Mean (+/- SEM) blood pressure was significantly higher than the control values (121 +/- 3 mm Hg) at the end of the study in rats with renal artery stenosis (178 +/- 13 mm Hg) and fructose-fed rats (151 +/- 5 mm Hg), whereas left ventricular weight was only significantly (P < .01) higher in rats with renal artery stenosis. Plasma glucose concentration was the same in all three groups, but fructose-fed rats had significantly higher plasma insulin (59 +/- 7 microU/mL) and TG (317 +/- 48 mg/dL) concentration than either sham-operated rats (30 +/- 4 microU/mL and 121 mg/dL) or rats with renal artery stenosis (34 +/- 5 microU/mL and 124 +/- 14 mg/dL). Although SSPI concentrations were similar (approximately 250 microU/mL) in all three groups of rats, SSPG concentrations were significantly higher (P < .01) in the fructose-fed rats (187 +/- 10 mg/dL) than in either sham-operated normotensive rats (120 +/- 6 mg/dL) or hypertensive rats with renal artery stenosis (133 +/- 4 mg/dL). Thus, insulin resistance, hyperinsulinemia, and hypertriglyceridemia developed in rats with fructose-induced hypertension, whereas none of these changes were seen in rats with renal artery stenosis.