Exercise training improves systolic function in hypertensive myocardium

The general purpose of this study was to test the effect of exercise training on the left ventricular (LV) pressure-volume relationship (LV/PV) and apoptotic signaling markers in normotensive and hypertensive hearts. Four-month-old female normotensive Wistar-Kyoto rats (WKY; n = 37) and spontaneously hypertensive rats (SHR; n = 38) were assigned to a sedentary (WKY-SED, n = 21; SHR-SED, n = 19) or treadmill-trained (WKY-TRD, n = 16; SHR-TRD, n = 19) group (～60% Vo(2 peak), 60 min/day, 5 days/wk, 12 wk). Ex vivo LV/PV were established in isovolumic Langendorff-perfused hearts, and LV levels of Akt, phosphorylated Akt (Akt(Pi)), Bad, phosphorylated Bad (Bad(Pi)) c-IAP, x-IAP, calcineurin, and caspases 3, 8, and 9 were measured. Heart-to-body weight ratio was increased in SHR vs. WKY (P < 0.05), concomitant with increased calcineurin mRNA (P < 0.05). There was a rightward shift in the LV/PV (P < 0.05) and a reduction in systolic elastance (E(s)) in SHR vs. WKY. Exercise training corrected E(s) in SHR (P < 0.05) but had no effect on the LV/PV in WKY. Caspase 3 was increased in SHR-SED relative to WKY-SED, while Bad(Pi,) c-IAP, and x-IAP were significantly lower in SHR relative to WKY (P < 0.05). Exercise training increased Bad(Pi) in both WKY and SHR but did not alter caspase 9 activity in either group. While caspase 3 activity was increased with training in WKY (P < 0.05), it was unchanged with training in SHR. We conclude that moderate levels of regular aerobic exercise attenuate systolic dysfunction early in the compensatory phase of hypertrophy, and that a differential phenotypical response to moderate-intensity exercise exists between WKY and SHR.     

Effects of forskolin on inotropic performance and phospholamban phosphorylation in exercise-trained hypertensive myocardium.

Beta-adrenergic receptor (beta-AR) responsiveness is downregulated in left ventricular (LV) hypertrophy induced by chronic hypertension. While exercise training in hypertension enhances beta-AR responsiveness, the role of adenylyl cyclase remains unclear. The purpose of the present study was to test whether treadmill running in the spontaneously hypertensive rat (SHR) model improves LV responsiveness to forskolin (FOR) or the combination of FOR + isoproterenol (FOR+ISO). Female SHR (16-wk) were randomly placed into sedentary (SHR-SED; n = 7) or treadmill-trained (SHR-TRD; n = 8) groups. Wistar-Kyoto (WKY; n = 7) animals acted as normotensive controls. Langendorff, isovolumic LV performance was established at baseline and during incremental FOR infusion (1 and 5 micromol/l) and FOR+ISO (5 micromol/l + 1x10(-8) mol/l). Heart rate, systolic blood pressure, and heart-to-body weight ratio were lower in WKY relative to both SHR groups (P < 0.05). LV performance and heart rate significantly increased in all groups to a similar extent with incremental FOR infusion. However, in the presence of 5 micromol/l FOR, ISO increased LV developed pressure, positive change in LV pressure, and negative change in LV pressure to a greater extent in SHR-TRD relative to SHR-SED (P < 0.05). Phospholamban phosphorylation at the Thr17 was greater in SHR-TRD relative to SHR-SED and WKY (P < 0.05). Absolute LV developed pressure was moderately correlated with phospholamban phosphorylation at both the Ser16 (r = 0.64; P < 0.05) and Thr17 (r = 0.52; P < 0.05). Our data suggest that the adenylyl cyclase step in the beta-AR cascade is not downregulated in the early course of hypertension and that the enhanced beta-AR responsiveness with training is likely mediated at levels other than adenylyl cyclase. Our data also suggest that beta-AR inotropic responsiveness in the presence of direct adenylyl cyclase agonism is improved in trained compared with sedentary SHR hearts.     

Myocardial hypoperfusion/reperfusion tolerance with exercise training in hypertension.

The purpose of this study was to examine whether exercise training, superimposed on compensated-concentric hypertrophy, could increase myocardial hypoperfusion-reperfusion (H/R) tolerance. Female Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) (age: 4 mo; N = 40) were placed into a sedentary (SED) or exercise training (TRD) group (treadmill running; 25 m/min, 1 h/day, 5 days/wk for 16 wk). Four groups were studied: WKY-SED (n = 10), WKY-TRD (n = 10), SHR-SED (n = 10), and SHR-TRD (n = 10). Blood pressure and heart rate were determined, and in vitro isolated heart performance was measured with a retrogradely perfused, Langendorff isovolumic preparation. The H/R protocol consisted of a 75% reduction in coronary flow for 17 min followed by 30 min of reperfusion. Although the rate-pressure product was significantly elevated in SHR relative to WKY, training-induced bradycardia reduced the rate-pressure product in SHR-TRD (P < 0.05) without an attenuation in systolic blood pressure. Heart-to-body weight ratio was greater in both groups of SHR vs. WKY-SED (P < 0.001). Absolute and relative myocardial tolerance to H/R was greater in WKY-TRD and both groups of SHR relative to WKY-SED (P < 0.05). Endurance training superimposed on hypertension-induced compensated hypertrophy conferred no further cardioprotection to H/R. Postreperfusion 72-kDa heat shock protein abundance was enhanced in WKY-TRD and both groups of SHR relative to WKY-SED (P < 0.05) and was highly correlated with absolute left ventricular functional recovery during reperfusion (R2= 0.86, P < 0.0001). These data suggest that both compensated hypertrophy associated with short-term hypertension and endurance training individually improved H/R and that increased postreperfusion 72-kDa heat shock protein abundance was, in part, associated with the cardioprotective phenotype observed in this study.     

Coronary vasodilator reserve, capillarity, and mitochondria in trained hypertensive rats

To test the hypothesis that exercise training can reverse the decrements in coronary reserve, capillary density, and mitochondrial volume density evident during established hypertension, we trained spontaneously hypertensive (SHR) and normotensive (WKY) rats on a treadmill over a 3-mo period. At 7 mo of age we used microspheres to evaluate myocardial perfusion in conscious rats. Exercise training did not alter hypertension or left ventricular hypertrophy but did increase maximal O2 consumption in both SHR and WKY. A decrement in left and right ventricular coronary reserve in SHR, compared with WKY, was indicated by 1) a smaller increment in myocardial perfusion during maximal vasodilation with dipyridamole and 2) a higher minimal coronary vascular resistance per unit mass. Exercise training had no significant effect on any index of myocardial perfusion in SHR or WKY. A 12% decrement in capillary numerical density in the endomyocardium of SHR was not reversed by exercise training. We estimated the volume densities of mitochondria, myofibrils, and sarcoplasm using electron microscopy and point-counting stereology on perfusion-fixed hearts. None of the parameters in either SHR or WKY was changed by exercise training. It is concluded that exercise training does not reverse the decrements in coronary reserve and capillary numerical density associated with hypertension in adult rats. Moreover the previously observed enhancement of mitochondrial volume density due to exercise in young hypertensive rats was not observed in adult SHR.     

Long-term left ventricular echocardiographic follow-up of SHR and WKY rats: effects of hypertension and age

Long-term follow-up of left ventricular (LV) function using echocardiography has not been reported and, in this study, was carried out in normotensive (WKY) rats and spontaneously hypertensive rats (SHR). In 10 WKY rats and SHR, LV diastolic and systolic diameter (LVEDD and LVSD), shortening fraction (SF), and weight (LVW) were determined at 8, 15, 20, 35, and 80 wk of age. The ratio of early to late mitral flow and mitral annulus velocity (VE/VA and Em/Am), isovolumic relaxation time (IVRT), deceleration time of the E wave (DTE), Tei index, and mitral flow propagation velocity (Vp) were measured. No difference in LVEDD was found between SHR and WKY rats; however, LVEDD was increased at 80 wk in both strains. SF decreased slightly in old WKY rats. LVW progressively increased from 20 to 80 wk in both strains and was greater in SHR. VE/VA and Em/Am decreased at 80 wk in WKY rats. LV relaxation (IVRT, Tei index, and Vp) was progressively impaired in SHR compared with WKY rats. LV compliance (DTE) was altered in old SHR. Echocardiography permitted a long follow-up of LV function in SHR and WKY rats. Ventricular relaxation was impaired early in the life of SHR and progressed with aging. Furthermore, LV compliance was altered, but systolic function remained unchanged, in old SHR. In contrast, relaxation and SF were only slightly altered in old WKY rats, suggesting that pressure-related changes in LV function were the dominant features in the SHR.     

Gender and aging in a transgenic mouse model of hypertrophic cardiomyopathy

Mutations in the cardiac myosin heavy chain (MHC) can cause familial hypertrophic cardiomyopathy (FHC). A transgenic mouse model has been developed in which a missense (R403Q) allele and an actin-binding deletion in the alpha-MHC are expressed in the heart. We used an isovolumic left heart preparation to study the contractile characteristics of hearts from transgenic (TG) mice and their wild-type (WT) littermates. Both male and female TG mice developed left ventricular (LV) hypertrophy at 4 mo of age. LV hypertrophy was accompanied by LV diastolic dysfunction, but LV systolic function was normal and supranormal in the young TG females and males, respectively. At 10 mo of age, the females continued to present with LV concentric hypertrophy, whereas the males began to display LV dilation. In female TG mice at 10 mo of age, impaired LV diastolic function persisted without evidence of systolic dysfunction. In contrast, in 10-mo-old male TG mice, LV diastolic function worsened and systolic performance was impaired. Diminished coronary flow was observed in both 10-mo-old TG groups. These types of changes may contribute to the functional decompensation typically seen in hypertrophic cardiomyopathy. Collectively, these results further underscore the potential utility of this transgenic mouse model in elucidating pathogenesis of FHC.     

Comparison of effects of exercise and diuretic on left ventricular geometry, mass, and insulin resistance in older hypertensive adults

To compare the effects of exercise training and hydrochlorothiazide on left ventricular (LV) geometry and mass, blood pressure (BP), and hyperinsulinemia in older hypertensive adults, we studied 28 patients randomized either to a group (age 66.4 +/- 1.3 yr; n = 16) that exercised or to a group (age 65.3 +/- 1.2 yr; n = 12) that received hydrochlorothiazide for 6 mo. Endurance exercise training induced a 15% increase in peak aerobic power. The reduction in systolic BP was twofold greater with thiazide than with exercise (26.6 +/- 12.2 vs. 11.5 +/- 10.9 mmHg). Exercise and thiazide reduced LV wall thickness, LV mass index (14% in each group), and the LV wall thickness-to-radius ratio (h/r) similarly (exercise: before 0.48 +/- 0.2, after 0.42 +/- 0.01; thiazide: before 0.47 +/- 0.04, after 0.40 +/- 0.04; P = 0.017). The reductions in systolic BP and h/r were correlated in the exercise group (r = 0.70, P = 0.005) but not in the thiazide group. Exercise training reduced glucose-stimulated hyperinsulinemia (before: 13.65 +/- 2.6 vs. 9.84 +/- 1.5 mU.ml(-1).min; P = 0.04) and insulin resistance. Thiazide did not affect plasma insulin levels. The results suggest that although exercise is less effective in reducing systolic BP than thiazide, it can induce regression of LV hypertrophy similar in magnitude to thiazide. Unlike hydrochlorothiazide, exercise training can improve insulin resistance and aerobic capacity in older hypertensive people.     

Myocardial hypertrophy of normotensive Wistar-Kyoto rats

In our studies with spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Wistar rats, we observed normotensive WKY rats with cardiac hypertrophy determined by a greater left ventricular (LV) mass (LVM)-to-body weight (BW) ratio (LVM/BW) than that of normotensive Wistar rats. Thus we compared the following parameters in SHR, WKY, and Wistar rats: LVM/BW, cell capacitance as index of total surface area of the myocytes, length, width, and cross-sectional area of cardiac myocytes, LV collagen volume fraction, and myocardial stiffness. The LVM/BW of WKY (2.41 +/- 0.03 mg/g, n = 41) was intermediate between SHR (2.82 +/- 0.04 mg/g, n = 47) and Wistar rats (1.98 +/- 0.04 mg/g, n = 28). A positive correlation between blood pressure and LVM was found in SHR, whereas no such relationship was observed in WKY or Wistar rats. Cell capacitance and cross-sectional area were not significantly different in SHR and WKY rats; these values were significantly higher than those of Wistar rats. The cell length was smaller but the width was similar in WKY compared with SHR. Papillary muscles isolated from the LV of WKY and SHR were stiffer than those from Wistar rats. Consistently, a greater level of myocardial fibrosis was detected in WKY and SHR compared with Wistar rats. These findings demonstrate blood pressure-independent cardiac hypertrophy in normotensive WKY rats.     

Reduction of ventricular hypertrophy and fibrosis in spontaneously hypertensive rats by L-arginine

The purpose of this experiment was to explore long-term L-arginine administration on ventricular hypertrophy and cardiac fibrosis in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats. Twenty-four rats of each strain at eight wks of age were divided into two groups--one receiving L-arginine and the other vehicle for twelve wks. Arterial pressure (AP) and heart rate were monitored. At 20 wks of age, the rats' rings of thoracic aorta were isolated to record isometric tension. The study measured left ventricular weight (LVW), body weight (BW), left ventricular (LV) contents of cGMP, and collagen volume fraction (LVCVF). Histological examination of the LV tissue determined changes in cardiomyocytes. Administration of L-arginine did not alter the AP change in SHR, but reduced the AP in WKY after six wks. Our results showed a significantly higher LVW/BW ratio and LVCVF in vehicle-treated SHR compared to levels in corresponding WKY, whereas, the LV cGMP and nitrite/nitrate measurements were higher in vehicle-treated WKY than in SHR. L-Arginine treatment decreased LVW/BW ratio and LVCVF, while increasing the levels of LV cGMP and nitrite/nitrate only in SHR, consistent with histopathological examinations that showed L-arginine prevented cardiomyocytes from thickness and hypertrophy. Our results suggested that the mechanism of reduction in ventricular hypertrophy and fibrosis following long-term L-arginine administration in SHR may stem from increased myocardial nitric oxide-cGMP signaling, independent of AP and EDV of thoracic aorta.     

Kallikrein gene delivery attenuates cardiac remodeling and promotes neovascularization in spontaneously hypertensive rats

Hypertension that results in left ventricular (LV) hypertrophy and/or fibrosis can lead to cardiac dysfunction. Spontaneously hypertensive rats (SHR) develop high blood pressure and LV hypertrophy at an early age and are a popular model of human essential hypertension. To investigate the role of the tissue kallikrein-kinin system in cardiac remodeling, an adenovirus containing the human tissue kallikrein gene was injected intravenously into adult SHR and normotensive Wistar-Kyoto (WKY) rats. The blood pressure of WKY rats remained unchanged throughout the experiment. Alternatively, kallikrein gene transfer reduced blood pressure in SHR for the first 2 wk, but had no effect from 3 to 5 wk. Five weeks after kallikrein gene delivery, SHR showed significant reductions in LV-to-heart weight ratio, LV long axis, and cardiomyocyte size; however, these parameters were unaffected in WKY rats. Interestingly, cardiac collagen density was decreased in both SHR and WKY rats receiving the kallikrein gene. Kallikrein gene transfer also increased cardiac capillary density in SHR, but not in WKY rats. The morphological changes after kallikrein gene transfer were associated with decreases in JNK activation as well as transforming growth factor (TGF)-beta 1 and plasminogen activator inhibitor-1 levels in the heart. In addition, kallikrein gene delivery elevated LV nitric oxide and cGMP levels in both rat strains. These results indicate that kallikrein-kinin attenuates cardiac hypertrophy and fibrosis and enhances capillary growth in SHR through the suppression of JNK, TGF-beta 1, and plasminogen activator inhibitor-1 via the nitric oxide-cGMP pathway.     

Effect of swimming training on cardiac function and myosin ATPase activity in SHR

Male spontaneously hypertensive rats (SHR) and Wistar-Kyoto normotensive rats (WKY) were subjected to swimming training 6 times/wk, commencing at 4 wk of age, to determine whether this type of endurance exercise might alter contractile proteins and cardiac function in young adult SHR. The total duration of exercise was 190 h. Myofibrillar adenosinetriphosphatase (ATPase) activity was assayed at various free [Ca2+] ranging from 10(-7) to 10(-5) M. Ca2+-stimulated ATPase activity of actomyosin and purified myosin was determined at various Ca2+ concentrations both in the low and high ionic strength buffers. Actin-activated myosin ATPase activity of purified myosin was assayed at several concentrations of actin purified from rabbit skeletal muscle. Under all these conditions the contractile protein ATPase activity was comparable between trained and untrained WKY and SHR. Analysis of myosin isoenzymes on pyrophosphate gels showed a single band corresponding to V1 isoenzyme, and there were no differences between swimming-trained and nontrained WKY and SHR. Ventricular performance was assessed by measuring cardiac output and stroke volume after rapid intravenous volume overloading. Both cardiac index and stroke index were comparable in nontrained WKY and SHR but were significantly increased in the trained groups compared with their respective nontrained controls. These results suggest that myosin ATPase activity and distribution of myosin isoenzymes are not altered in the moderately hypertrophied left ventricle whether the hypertrophy is due to genetic hypertension (SHR) or to exercise training (trained WKY). Moreover, the data indicate that SHR, despite the persistence of a pressure overload, undergo similar increases in left ventricular mass and peak cardiac index after training, as do normotensive WKY.     

Chronic beta-adrenoreceptor activation increases cardiac cavity size through chamber remodeling and not via modifications in myocardial material properties

Chronic beta-adrenoreceptor (beta-AR) activation increases left ventricular (LV) cavity size by promoting a rightward shift in LV diastolic pressure-volume (P-V) relations in association with increases in low-tensile strength myocardial (non-cross-linked) collagen concentrations. Because diastolic P-V relations are determined by chamber remodeling as well as by myocardial material properties (indexed by myocardial stiffness), both of which are associated with modifications in myocardial collagen cross-linking, we evaluated whether chamber remodeling or alterations in myocardial material properties govern beta-AR-mediated modifications in diastolic P-V relations. The effects of chronic administration of isoproterenol (Iso; 0.04 mg.kg(-1).day(-1) from 12 to 19 mo of age) to spontaneously hypertensive rats (SHRs) on LV cavity dimensions, LV diastolic P-V relations, myocardial collagen characteristics, myocardial stiffness constants [e.g., the slope of the LV diastolic stress-strain relation (k)], and LV chamber and myocardial systolic function were assessed. SHRs at 19 mo of age had normal LV diastolic P-V relations, marked myocardial fibrosis (using a pathological score), increased myocardial cross-linked (insoluble to cyanogen bromide digestion) type I and type III collagen concentrations, and enhanced myocardial k values. Iso administration to SHRs resulted in enlarged LV cavity dimensions mediated by a rightward shift in LV diastolic P-V relations, increased volume intercept of the LV diastolic P-V relation, decreased LV relative wall thickness despite a tendency to augment LV hypertrophy, and increased non-cross-linked type I and type III myocardial collagen concentrations. Iso administration resulted in reduced pump function without modification of intrinsic myocardial systolic function. However, despite increasing myocardial non-cross-linked concentrations, Iso failed to alter myocardial k in SHRs. These results suggest that beta-AR-mediated rightward shifts in LV diastolic P-V relations, which induce decreased pump function, are mediated by chamber remodeling but not by modifications in myocardial material properties.     

Adaptations in beta-adrenergic cardiovascular responses to training in older women.

To determine whether endurance exercise training can alter the beta-adrenergic-stimulated inotropic response in older women, we studied 10 postmenopausal healthy women (65.4 +/- 0.9 yr old) who exercised for 11 mo. Left ventricular (LV) function was evaluated with two-dimensional echocardiography during infusion of isoproterenol after atropine. Maximal O(2) consumption increased 23% in response to training (from 1.35 +/- 0.06 to 1.66 +/- 0.07 l/min; P = 0.004). Training had no effect on baseline LV function, end-diastolic diameter, LV wall thickness, or LV mass. The increase in LV systolic function in response to isoproterenol was unaffected by training. Furthermore, neither the systolic shortening-to-end-systolic wall stress relationship nor the end-systolic wall stress-to-end-systolic diameter relationship during isoproterenol infusion changed with training. We conclude that older postmenopausal women can increase their maximal O(2) consumption with exercise training without eccentric LV hypertrophy or enhancement of beta-adrenergic-mediated LV contractile function. These observations provide an explanation for the finding that maximal cardiac output and stroke volume are not increased in older women in response to training.     

Moderate exercise training does not worsen left ventricle remodeling and function in untreated severe hypertensive rats.

Exercise training and hypertension induced cardiac hypertrophy but modulate differently left ventricle (LV) function. This study set out to evaluate cardiac adaptations induced by moderate exercise training in normotensive and untreated severe hypertensive rats. Four groups of animals were studied: normotensive (Ctl) and severe hypertensive (HT) Wistar rats were assigned to be sedentary (Sed) or perform a moderate exercise training (Ex) over a 10-wk period. Severe hypertension was induced in rat by a two-kidney, one-clip model. At the end of the training period, hemodynamic parameters and LV morphology and function were assessed using catheterism and conventional pulsed Doppler echocardiography. LV histology was performed to study fibrosis infiltrations. Severe hypertension increased systolic blood pressure to 202 +/- 9 mmHg and induced pathological hypertrophy (LV hypertrophy index was 0.34 +/- 0.02 vs. 0.44 +/- 0.02 in Ctl-Sed and HT-Sed groups, respectively) with LV relaxation alteration (early-to-atrial wave ratio = 2.02 +/- 0.11 vs. 1.63 +/- 0.12). Blood pressure was not altered by exercise training, but arterial stiffness was reduced in trained hypertensive rats (pulse pressure was 75 +/- 7 vs. 62 +/- 3 mmHg in HT-Sed and HT-Ex groups, respectively). Exercise training induced eccentric hypertrophy in both Ex groups by increasing LV cavity without alteration of LV systolic function. However, LV hypertrophy index was significantly decreased in normotensive rats only (0.34 +/- 0.02 vs. 0.30 +/- 0.02 in Ctl-Sed and Ctl-Ex groups, respectively). Moreover, exercise training improved LV passive filling in Ctl-Ex rats but not in Ht-Ex rats. In this study, exercise training did not reduce blood pressure and induced an additional physiological hypertrophy in untreated HT rats, which was slightly blunted when compared with Ctl rats. However, cardiac function was not worsened by exercise training.     

Validation of echocardiographic and Doppler indexes of left ventricular relaxation in adult hypertensive and normotensive rats

This study was performed to validate echocardiographic and Doppler techniques for the assessment of left ventricular (LV) diastolic function in spontaneously hypertensive rats (SHR) and normotensive Wistar rats. In 11 Wistar rats and 20 SHR, we compared 51 sets of invasive and Doppler LV diastolic indexes. Noninvasive indexes of LV relaxation were related to the minimal rate of pressure decline (-dP/dt(min)), particularly isovolumic relaxation time (IVRT), the Tei index, the early velocity of the mitral annulus (E(m)) using Doppler tissue imaging, and early mitral flow propagation velocity using M-mode color (r = 0.28-0.56 and P < 0.05-0.0001). When the role of systolic load was considered, the correlation between Doppler indexes of LV diastolic function and relaxation rate [(-dP/dt(min))/LV systolic pressure] improved (r = 0.48-0.86 and P = 0.004-0.0001, respectively). Similarly, Doppler indexes of LV diastolic function and the time constant of isovolumic LV relaxation (tau) correlated well (r = 0.50-0.84 and P = 0.0002-0.0001, respectively). In addition, eight SHR and eight Wistar rats were compared; their LV end-diastolic diameters were similar, whereas the SHR LV mass was greater. Furthermore, IVRT and Tei index were significantly higher and E(m) was lower in SHR. Moreover, tau was higher in SHR, demonstrating impaired LV relaxation. In conclusion, LV relaxation can be assessed reliably using echocardiographic and Doppler techniques, and, using these indexes, impaired relaxation was demonstrated in SHR.     

Arsenic contamination of groundwater and prevalence of arsenical dermatosis in the Hetao plain area,Inner Mongolia,China

The present study determined cardiac chamber-specific alterations of the expression of the atrial and brain natriuretic peptide (ANP and BNP) genes with a small increase in age beyond adulthood and with systemic hypertension of intermediate duration. The expression distributions of these genes was determined using in situ hybridization in the right and left atria (RA and LA), and the right and left ventricles (RV and LV) in Wistar Kyoto rats (WKY) and age-matched Spontaneously Hypertensive rats (SHR) at ages 6 months (adult) and 8 months (advanced-age beyond adulthood).In all rat groups, both genes were expressed (ANP > BNP) in the LA and LV, and were not expressed in the RA and RV. The genes were expressed in the LA in all rat groups; the ANP, but not the BNP, expression increased with advancing age and with superimposed hypertension. They were expressed in the LV of the advanced-age WKY, adult and advanced-age SHR, but not in the adult WKY. The ANP mRNA labeling in the LA was diffuse and interspersed with dense accumulations, whereas BNP labeling was diffuse. The labeling of both genes in the form of sparse clusters was seen in the LV of the advanced-age SHR. Our study showed that ANP and BNP expression in left heart chambers increased with a small increase in age, with hypertension of intermediate duration, and with modest left ventricular hypertrophy. The chamber-specific expression distribution could be due to special groups of cardiac cells, or to local chamber-specific factors.     

Low‐intensity aerobic exercise improves cardiac remodelling of adult spontaneously hypertensive rats

We evaluated the influence of aerobic training on cardiac remodeling in untreated spontaneously hypertensive rats (SHR). Four experimental groups were used: sedentary (W‐SED, n=27) and trained (WEX, n=31) normotensive Wistar rats, and sedentary (SHR‐SED, n=27) and exercised (SHR‐EX, n=32) hypertensive rats. At 13 months old, trained groups underwent treadmill exercise five days a week for four months. Statistical analysis: ANOVA or Kruskal‐Wallis. Exercised groups had higher physical capacity. Hypertensive groups presented left ventricular (LV) concentric hypertrophy with impaired function. Left atrium diameter, LV posterior wall thickness and relative thickness, and isovolumetric relaxation time were lower in SHR‐EX than SHR‐SED. Interstitial collagen fraction and Type I‐Type III collagen ratio were higher in SHR‐SED than W‐SED. In SHR‐EX these parameters had intermediate values between W‐EX and SHRSED with no differences between either group. Myocardial matrix metalloproteinase‐2 activity, evaluated by zymography, was higher in SHR‐SED than W‐SED and SHR‐EX. TIMP‐2 was higher in hypertensive than normotensive groups. In conclusion, low intensity aerobic exercise reduces left atrium dimension and LV posterior wall thickness, and improves functional capacity, diastolic function, and metalloproteinase‐2 activity in adult SHR.     

Increased sympathetic innervation in the cerebral and mesenteric arteries of hypertensive rats

The density of catecholamine-containing nerve fibers was studied in the cerebral and mesenteric arteries from normotensive Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR), and stroke-prone SHR (SHRSP) in the growing (SHR, WKY) and adult (SHR, SHRSP, WKY) animals. Cerebral arteries from SHR showed an increased adrenergic innervation from day 1. The nerve plexuses reached an adult pattern earlier in SHR than in WKY. The arteries from adult SHR and SHRSP (22 weeks old) showed a markedly higher nerve density than WKY. There was a positive linear correlation between blood pressure and nerve density for four cerebral arteries. The mesenteric arteries were not innervated at birth. However, hyperinnervation of these arteries in the SHR was already present at 10 days of age as compared with WKY. Sympathectomy with anti-nerve growth factor and guanethidine caused a complete disappearance of fluorescent fibers in the mesenteric arteries from SHR and WKY, and in the cerebral arteries of WKY. The same procedure caused only partial denervation of the cerebral arteries from hypertensive animals. We postulate that the increase in nerve density in the cerebral arteries from the hypertensive rats may contribute to the development of arterial hypertrophy in chronic hypertension through the trophic effect of the sympathetic innervation on vascular structure.