Increased renal resistive index in patients with essential hypertension: a marker of target organ damage.
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BACKGROUND: Increased renal resistance detected by ultrasound (US) Doppler has been reported in severe essential hypertension (EH) and recently was shown to correlate with the degree of renal impairment in hypertensive patients with chronic renal failure. However, the pathophysiological significance of this finding is still controversial. METHODS: In a group of 211 untreated patients with EH, we evaluated renal resistive index (RI) by US Doppler of interlobar arteries and early signs of target organ damage (TOD). Albuminuria was measured as the albumin to creatinine ratio (ACR) in three non-consecutive first morning urine samples. Left ventricular mass was evaluated by M-B mode echocardiography, and carotid wall thickness (IMT) by high resolution US scan. RESULTS: RI was positively correlated with age (r=0.25, P=0.003) and systolic blood pressure (SBP) (r=0.2, P=0.02) and with signs of early TOD, namely ACR (r=0.22, P=0.01) and IMT (r=0.17, P<0.05), and inversely correlated with renal volume (r=-0.22, P=0.01) and diastolic blood pressure (r=-0.23, P=0.006). Multiple linear regression analysis demonstrated that age, gender, ACR and SBP independently influence RI and together account for approximately 20% of its variations (F=8.153, P<0.0001). When clinical data were analysed according to the degree of RI, the patients in the top quartile were found to be older (P<0.05) and with higher SBP (P<0.05) as well as early signs of TOD, namely increased ACR (P<0.002) and IMT (P<0.005 by ANOVA), despite similar body mass index, uric acid, fasting blood glucose, lipid profile and duration of hypertension. Furthermore, patients with higher RI showed a significantly higher prevalence of microalbuminuria (13 vs 12 vs 3 vs 33% chi2=11.72, P=0.008) and left ventricular hypertrophy (40 vs 43 vs 32 vs 60%, chi2=9.25, P<0.05). CONCLUSIONS: Increased RI is associated with early signs of TOD in EH and could be a marker of intrarenal atherosclerosis. (+info)
Inhibition of beta-myosin heavy chain gene expression in pressure overload rat heart by losartan and captopril.
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AIM: To study the effects of losartan and captopril on beta-myosin heavy chain (MHC), and alpha-MHC gene expression. METHODS: Pressure overload was produced by abdominal aortic coarctation (AAC) in rats. alpha- and beta-MHC mRNA were measured by Northern blot. RESULTS: In left ventricular myocardium of sham-operated rats, the alpha-MHC mRNA predominated, while the beta-MHC mRNA was only detectable. In response AAC, there was a 70-fold increase in the beta-MHC mRNA (P < 0.01), while alpha-MHC mRNA reduced to 26% (P < 0.01). Losartan (3 mg.kg-1.d-1, i.g. for 11 d) to AAC rats caused inhibitions of beta-MHC by 96% and alpha-MHC by 86% gene expression without lowering blood pressure. A reduction in beta-MHC mRNA was also seen in captopril-treated rats (30 mg.kg-1.d-1, i.g. for 11 d), but the inhibitory effect of captopril on alpha-MHC mRNA was less than that of losartan (44% vs 86%, P < 0.05). CONCLUSIONS: The shift of MHC isoform induced by pressure overload is due to up-regulation of beta-MHC and down-regulation of alpha-MHC gene expression. Inhibition of beta-MHC gene expression by losartan is achieved primarily by direct blockade of angiotensin II type I receptors in the myocardium, independent on hemodynamics. (+info)
Effects of praeruptorine C on the intracellular free calcium in normal and hypertrophied rat ventricular myocytes.
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AIM: To study the intracellular free calcium ([Ca2+]i) in normal and hypertrophic left ventricular myocytes isolated from adult rat hearts and the effects of praeruptorine C (Pra-C) on them. METHODS: [Ca2+]i of single myocyte was measured with Fura 2-AM. RESULTS: The resting [Ca2+]i was 87 +/- 4 nmol.L-1 in normal left ventricular myocytes, 123 +/- 7 nmol.L-1 in hypertrophied myocytes. After exposure to KCl (20, 40, and 60 mmol.L-1), the [Ca2+]i were increased by 66%, 141%, and 268% in normal myocytes, and 77%, 185%, and 243% in hypertrophic myocytes, respectively. Pra-C (1, 10, and 100 mumol.L-1) concentration-dependently inhibited the [Ca2+]i elevation caused by KCl (35 mmol.L-1) or norepinephrine (20 mumol.L-1) in both normal and hypertrophied myocytes. All of the effects of Pra-C were similar to that of nifedipine. CONCLUSION: [Ca2+]i of hypertrophied myocytes was higher than that of normal ones and Pra-C decrease the [Ca2+]i elevation in left ventricular myocytes resulted from its calcium channel blockade. (+info)
Modification of left ventricular hypertrophy by chronic etomixir treatment.
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1. Etomoxir (2[6(4-chlorophenoxy)hexyl]oxirane-2-carboxylate), an irreversible carnitine palmitoyl-transferase 1 inhibitor, reduces the expression of the myocardial foetal gene programme and the functional deterioration during heart adaption to a pressure-overload. Etomoxir may, however, also improve the depressed myocardial function of hypertrophied ventricles after a prolonged pressure overload. 2. To test this hypothesis, we administered racemic etomoxir (15 mg kg(-1) day(-1) for 6 weeks) to rats with ascending aortic constriction beginning 6 weeks after imposing the pressure overload. 3. The right ventricular/body weight ratio increased (P<0.05) by 20% in etomoxir treated rats (n = 10) versus untreated rats with ascending aortic constriction (n = 10). Left ventricular weight was increased (P<0.05) by 8%. Etomoxir blunted the increase in left ventricular chamber volume. Etomoxir raised the proportion of V1 isomyosin (35+/-4% versus 24+/-2%; P<0.05) and decreased the percentage of V3 isomyosin (36+/-4% versus 48+/-3%; P<0.05). 4. Maximum isovolumically developed pressure was higher in etomoxir treated rats than in untreated pressure overloaded rats (371+/-22 versus 315+/-23 mmHg; P<0.05). Maximum rates of ventricular pressure development (14,800+/-1310 versus 12,340+/-1030mmHg s(-1); P<0.05) and decline (6440+/-750 versus 5040+/-710 mmHg s(-1); P<0.05) were increased as well. Transformation of pressure values to ventricular wall stress data revealed an improved myocardial function which could partially account for the enhanced function of the whole left ventricle. 5. The co-ordinated action of etomoxir on ventricular mass, geometry and myocardial phenotype enhanced thus the pressure generating capacity of hypertrophied pressure-overloaded left ventricles and delayed the deleterious dilative remodelling. (+info)
Assessment of arterial compliance by carotid midwall strain-stress relation in hypertension.
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To elucidate the relations between arterial hypertrophy and compliance in hypertension, we studied 205 unmedicated hypertensive patients (129 men and 76 women) and 82 normotensive adults (56 men and 26 women) from an employed population by carotid ultrasound, noninvasive applanation tonometry, and echocardiography. Carotid midwall strain and circumferential stress were calculated at end diastole and peak systole. The relations of luminal and midwall strain to the increment in circumferential stress from end diastole to peak systole (Deltacarotid stress in normal subjects) were used to calculate ratios of observed/predicted carotid luminal and midwall strain. Mean stress-corrected luminal strain (82+/-26%) and midwall strain (78+/-23%) were lower (both P<0.001) in hypertensive patients than in normal adults. Stress-corrected luminal strain identified 14% of hypertensive patients with low arterial compliance, while stress-corrected midwall strain was low in 18% of patients. Patients with subnormal carotid midwall strain were older (61+/-12 versus 54+/-12 years, P<0.01) and had larger carotid diameters (6. 6+/-0.8 versus 5.7+/-0.8 mm, P=0.002) and higher brachial pulse pressures (71+/-25 versus 63+/-17 mm Hg, P<0.05) than other patients. Patients with arterial hypertrophy had lower stress-corrected midwall strain than those without hypertrophy (70+/-24% versus 79+/-23%, P=0.05), whereas no difference was observed in stress-corrected luminal strain (P=0.40). Stress-corrected midwall strain tended to be lower in patients with discrete atherosclerotic plaques than in those without (74+/-20% versus 79+/-24%, P=0.15). Compared with patients with normal left ventricular geometry, those with concentric hypertrophy had larger carotid diameters (6.6+/-0.7 versus 5.8+/-0.9 mm, P<0.05) and lower stress-corrected luminal strain (62+/-11% versus 85+/-25%, P<0.05) and midwall strain (59+/-10% versus 81+/-22%, P<0.05). Therefore, stress-corrected midwall strain identifies patients with reduced arterial compliance, increased arterial wall thickness, and abnormal left ventricular geometry better than conventional measures based on arterial lumen diameters. (+info)
Stroke volume/pulse pressure ratio and cardiovascular risk in arterial hypertension.
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Ratio of stroke volume (SV, M-mode echocardiography) to pulse pressure (PP) has been proposed as an estimate of total arterial compliance and has been shown to be related to body size, age, and heart rate in normal adults. SV/PP was estimated in 294 hypertensive patients (98 women) as a raw value by use of SV/body surface area (SVi) and by the ratio of SV/PP to the value predicted by a previously developed equation (%SV/PP). At baseline, the 50 patients who had cardiovascular events over the following 10 years exhibited higher PP and lower SV/PP, SVi/PP, and %SV/PP (all P<0.008) than patients without events. Crude risk of follow-up total and fatal cardiovascular events increased with increasing level of PP and decreasing SV/PP, SVi/PP, and %SV/PP (all P<0.002). In multivariate logistic regression models with continuous covariates, the risk of total cardiovascular events was independently related to increasing age (P<0.0001) and left ventricular (LV) mass index (P<0.003) and decreasing values of %SV/PP (P<0.006) but not to increasing systolic, pulse, or mean blood pressure or gender. Similar although less strong results were obtained with the use of SVi/PP (P<0.02), whereas SV/PP did not enter the model as an independent predictor. Risk of cardiovascular death was only predicted by age and LV mass index. The %SV/PP was also an independent predictor of total cardiovascular events in Cox proportional hazards analysis (exp[b]: 2.49, P<0.001) independent of age (exp[b]: 1.05, P<0.003) and LV mass index (exp[b]: 1.02, P<0.0003), whereas no effect was detected for height. Thus, in patients with arterial hypertension, a reduced ratio of M-mode echocardiographic SV/PP as a percentage of the value predicted by demographic variables is a predictor of cardiovascular morbid events independent of age and LV mass index. (+info)
Decreased left ventricular filling pressure 8 months after corrective surgery in a 55-year-old man with tetralogy of Fallot: adaptation for increased preload.
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A 55-year-old man with tetralogy of Fallot underwent corrective surgery. Left ventricular filling pressure increased markedly with increased left ventricular volume one month after surgery, then decreased over the next 7 months, presumably due to increased left ventricular compliance. (+info)
Cell death in acromegalic cardiomyopathy.
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BACKGROUND: Prolonged untreated acromegaly leads to a nonspecific myopathy characterized by ventricular dysfunction and failure. However, the mechanisms responsible for the alterations of cardiac pump function remain to be defined. Because cell death is implicated in most cardiac disease processes, the possibility has been raised that myocyte apoptosis may occur in the acromegalic heart, contributing to the deterioration of ventricular hemodynamics. METHODS AND RESULTS: Ten acromegalic patients with diastolic dysfunction and 4 also with systolic dysfunction were subjected to electrocardiography, Holter monitoring, 2-dimensional echocardiography, cardiac catheterization, and biventricular and coronary angiography before surgical removal of a growth hormone-secreting pituitary adenoma. Endomyocardial biopsies were obtained and analyzed quantitatively in terms of tissue scarring and myocyte and nonmyocyte apoptosis. Myocardial samples from papillary muscles of patients who underwent valve replacement for mitral stenosis were used for comparison. The presence of apoptosis in myocytes and interstitial cells was determined by confocal microscopy with the use of 2 histochemical methods, consisting of terminal deoxynucleotidyl transferase (TdT) assay and Taq probe in situ ligation. Acromegaly was characterized by a 495-fold and 305-fold increase in apoptosis of myocytes and nonmyocytes, respectively. The magnitude of myocyte apoptosis correlated with the extent of impairment in ejection fraction and the duration of the disease. A similar correlation was found with the magnitude of collagen accumulation, indicative of previous myocyte necrosis. Myocyte death was independent from the hormonal levels of growth hormone and insulin-like growth factor-1. Apoptosis of interstitial cells did not correlate with ejection fraction. CONCLUSIONS: Myocyte cell death, apoptotic and necrotic in nature, may be critical for the development of ventricular dysfunction and its progression to cardiac failure with acromegaly. (+info)