ISSN:0194-911X    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Left ventricular (LV) hypertrophy and concentric remodeling have been defined by using a variety of indexation methods and partition values (PVs) for LV mass and relative wall thickness (RWT). The effects of these methods on the distribution of LV geometric patterns in hypertensive subjects remain unclear. Echocardiograms were obtained in 941 patients with stage I to III hypertension and LV hypertrophy by ECG. LV mass was calculated by using different methods of indexation for body size and different PVs to identify hypertrophy: LV mass/body surface area (g/m2) PV for men/women 116/104, 125/110, or 125/125; LV mass/height (g/m) PV 143/102 or 126/105; and LV mass/height2.7(g/m2.7) PV 51/51 or 49.2/46.7. RWT was calculated by either 2×end-diastolic posterior wall thickness (PWT)/end-diastolic LV internal dimension (LVID) or end-diastolic interventricular septum dimension+end-diastolic PWT/end-diastolic LVID. LV hypertrophy or remodeling was present in 63% to 86% of subjects, and LV hypertrophy was present in 42% to 77%. By any index, eccentric hypertrophy was the common LV geometric pattern. Use of interventricular septum dimension+PWT/LVID to calculate RWT slightly increased the prevalence of normal geometry and eccentric hypertrophy compared with the use of 2×PWT/LVID. Subjects with LV hypertrophy identified by only LV mass/height2.7PV 49.2/46.7 were more obese, whereas those identified by only LV mass/body surface area PV 116/104 were taller and thinner than those in the 2 concordant groups with or without LV hypertrophy by both criteria. By either criterion, there were no significant differences between different LV geometric patterns in clinical cardiovascular disease. Hypertensive patients with LV hypertrophy by ECG have a high prevalence of geometric abnormalities, especially eccentric hypertrophy, irrespective of method of indexation or PV. LV mass indexation by body surface area or height2.7identifies lean and obese subjects, respectively. We found no difference in prevalent cardiovascular disease in subjects identified by either criterion, suggesting a similar high risk.

ISSN:0194-911X    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Obesity may limit sensitivity of ECG voltage criteria for left ventricular hypertrophy (LVH) because of the attenuating effects of increased body mass on precordial voltages. However, obesity is associated with an increased prevalence of anatomic LVH, making more accurate ECG criteria in obese patients a clinical priority. ECG LVH by Cornell voltage-duration product and/or Sokolow-Lyon voltage criteria was used to select patients for the Losartan Intervention For Endpoint (LIFE) Reduction in Hypertension Study. Clinical and ECG data were available in 8417 patients (54% women; mean age, 67±7 years); 2519 were overweight and 1573 were obese by gender-specific body mass index criteria. Increased body mass index had significant but directionally opposite effects on ECG LVH by these 2 criteria. Compared with normal-weight patients, obese and overweight patients had lower Sokolow-Lyon voltage and a lower prevalence of ECG LVH by Sokolow-Lyon criteria (10.9% versus 16.2% versus 31.4%;P<0.001). In contrast, obese and overweight patients had higher mean values of the Cornell product and higher prevalences of ECG LVH by this criterion (75.1% versus 69.9% versus 60.7%;P<0.001). After adjustment for age, gender, race, myocardial infarction, and diastolic and pulse pressure with the use of logistic regression analysis, increased body mass remained highly predictive of the presence of ECG LVH. Compared with normal-weight patients, obese patients had a >2-fold higher risk of ECG LVH by the Cornell product but a 4-fold lower risk of ECG LVH by Sokolow-Lyon voltage; overweight status was associated with intermediate risks, with a 151% greater likelihood of ECG LVH by the Cornell product but only 44% of the risk of LVH by Sokolow-Lyon voltage criteria compared with normal-weight individuals. Thus, Sokolow-Lyon voltage criteria underestimate the prevalence of anatomic LVH in the presence of obesity, whereas Cornell product criteria for ECG LVH appear to provide a more accurate measure of LVH in obese and overweight patients.

ISSN:0194-911X    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Atrial natriuretic peptide (ANP) may function as an endogenous regulator of cardiac hypertrophy, because the natriuretic peptide receptor has been found in the heart and because mice lacking its receptor have been shown to have a markedly elevated ventricular mass. We examined the role of endogenous ANP in cardiac hypertrophy in vitro. The effects of the blockade of endogenous ANP by its receptor antagonist, HS-142–1, on cell hypertrophy were investigated with the use of cultured neonatal rat ventricular myocytes. HS-142–1 increased the basal and phenylephrine (PE, 10−5mol/L)–stimulated protein syntheses in a concentration-dependent manner (1 to 300 &mgr;g/mL). A significant increase in the cell size of myocytes was also induced by this antagonist. In addition, the expression levels of skeletal &agr;-actin, &bgr;-myosin heavy chain, and ANP genes, markers of hypertrophy, were partially elevated by treatment with HS-142–1 (100 &mgr;g/mL) under nonstimulated or PE-stimulated conditions. A cGMP-specific phosphodiesterase inhibitor, zaprinast (5×10−4mol/L), and a cGMP analogue (10−4mol/L) suppressed the basal and PE-stimulated protein syntheses. Our observations suggest that endogenous ANP inhibits cardiac myocyte hypertrophy under basal and PE-stimulated conditions, probably through a cGMP-dependent process. ANP may play a role as an autocrine factor in the regulation of cardiac myocyte growth.

ISSN:0194-911X    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The tissue kallikrein-kinin system is present in the heart, and kinin has been shown to have cardioprotective effects. In this study, we investigated the potential role of tissue kallikrein in myocardial ischemia/reperfusion injury through adenovirus-mediated human kallikrein gene delivery. One week after gene delivery, the rats were subjected to a 30-minute coronary occlusion followed by a 2-hour reperfusion. Kallikrein gene delivery caused significant decreases in the ratio of infarct size to ischemic area at risk (from 69.6% to 44.5%, n=10 and 8,P<0.01) and in the incidence of ventricular fibrillation (from 64.3% to 16.7%, n=14 and 24,P<0.01) compared with the group injected with control adenovirus. Kallikrein gene delivery also attenuated programmed cell death in the ischemic area compared with the control area as assessed with the terminal deoxynucleotidyl transferase–mediated nick end labeling assay (n=6,P<0.01). Icatibant, a specific bradykinin B2receptor antagonist, abolished these kallikrein-mediated beneficial effects. The expression of human tissue kallikrein mRNA was identified in rat heart, kidney, lung, liver, and adrenal gland. After kallikrein gene delivery, cardiac kinin and cGMP levels were significantly elevated compared with the control (29.6±12.7 versus 6.1±2.1 pg/mg protein, n=7,P<0.01; 1.30±0.06 versus 0.86±0.09 pmol/mg protein, n=5,P<0.05). These results indicate that kallikrein gene delivery protects against myocardial infarction, ventricular arrhythmias, and apoptosis in ischemia/reperfusion injury via kinin-cGMP signal pathway. The successful application of this technology may have potential therapeutic value in the treatment of coronary artery diseases.

ISSN:0194-911X    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Inhibitors of angiotensin I–converting enzyme (ACE) are very efficacious in the potentiation of the actions of bradykinin (BK) and are able to provoke a B2receptor–mediated vasodilation even after desensitization of this receptor. Because this activity cannot be easily explained only by an inhibition of kinin degradation, direct interactions of ACE inhibitors with the B2receptor or its signal transduction have been hypothesized. To clarify the significance of degradation-independent potentiation, we studied the vasodilatory effects of BK and 2 degradation-resistant B2receptor agonists in the isolated rat heart, a model in which ACE and aminopeptidase P (APP) contribute equally to the degradation of BK. Coronary vasodilation to BK and to a peptidic (B6014) and a nonpeptidic (FR190997) degradation-resistant B2agonist was assessed in the presence or absence of the ACE inhibitor ramiprilat, the APP inhibitor mercaptoethanol, or both. Ramiprilat or mercaptoethanol induced leftward shifts in the BK dose-response curve (EC50=3.4 nmol/L) by a factor of 4.6 or 4.9, respectively. Combined inhibition of ACE and APP reduced the EC50of BK to 0.18 nmol/L (ie, by a factor of 19) but potentiated the activity of B6014 (EC50=1.9 nmol/L) only weakly without altering that of FR190997 (EC50=0.34 nmol/L). Desensitization of B2receptors was induced by the administration of BK (0.2 &mgr;mol/L) or FR190997 (0.1 &mgr;mol/L) for 30 minutes; the vascular reactivity to ramiprilat or increasing doses of BK was tested thereafter. After desensitization with BK, but not FR190997, an additional application of ramiprilat provoked a B2receptor–mediated vasodilation. High BK concentrations were still effective at the desensitized receptor. The process of desensitization was not altered by ramiprilat. These results show that in this model, all potentiating actions of ACE inhibitors on kinin-induced vasodilation are exclusively related to the reduction in BK breakdown and are equivalently provoked by APP inhibition. The desensitization of B2receptors is overcome by increasing BK concentrations, either directly or through the inhibition of ACE. These observations do not suggest any direct interactions of ACE inhibitors with the B2receptor or its signal transduction but point to a very high activity of BK degradation in the vicinity of the B2receptor in combination with a stimulation-dependent reduction in receptor affinity.

ISSN:0194-911X    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Impaired receptor-stimulated adenylyl cyclase activation has been observed in lymphocytes from hypertensive subjects and has been linked to an increase in lymphocyte G-protein receptor kinase-2 (GRK-2) protein expression. However, whether the increase in lymphocyte GRK-2 reflected an increase in vascular GRK-2 was unknown. Therefore, we compared GRK-2 protein expression in lymphocytes and aortas obtained from normotensive Wistar rats, Wistar-Kyoto rats (WKY), and spontaneously hypertensive rats (SHR) and from aortas of Dahl rats. Impaired &bgr;-adrenergic responsiveness was observed in lymphocytes and vascular tissues obtained from hypertensive SHR (10 and 15 weeks old) but not in those obtained from prehypertensive SHR (5 weeks old). Immunodetectable lymphocyte GRK-2 protein expression was increased in 10-week-old SHR (143±10% of the expression in 10-week-old Wistar rats and 131±11% of the expression in 10-week-old WKY, n=5 in each group). Immunodetectable vascular smooth muscle cell GRK-2 was comparably increased (169±14% of the expression in Wistar rats and 138±7% of the expression in WKY, n=5 in each group). Also, in hypertensive Dahl salt-sensitive rats, vascular GRK-2 protein expression was increased (185±14% of the expression in Dahl salt-resistant rats, n=5 in each group) compared with Dahl salt-resistant controls. These studies support a generalized defect in vascular GRK-2 protein expression in hypertension, which could be an important factor in the impairment of &bgr;-adrenergic–mediated vasodilation, characteristic of the hypertensive state.

ISSN:0194-911X    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

We analyzed the influence of aging and genetic hypertension on the function and expression of soluble guanylyl cyclase (sGC) in the aortas of prehypertensive and old spontaneously hypertensive rats (SHR) as well as in age-matched normotensive Wistar-Kyoto rats (WKY). The expression of heterodimeric sGC (&agr;1and &bgr;1) was assessed at the mRNA and protein level, and its function was assessed by the relaxant responses of phenylephrine-contracted endothelium-denuded aortic rings to the nitric oxide (NO) donor sodium nitroprusside. The vasodilator potency of sodium nitroprusside was significantly reduced (P<0.05) with age (3- to 6-fold increase in the EC50in old WKY and SHR compared with their young counterparts) as well as with hypertension (3-fold increase in old SHR compared with age-matched WKY), whereas the vasodilator potency of sodium nitroprusside did not differ between young SHR and WKY. A similar influence of aging and hypertension on NO-stimulated GC activity was revealed at the GC expression level: Whereas the &bgr;1protein content was similar in young rats of both strains, old WKY exhibited 60% lower and old SHR exhibited 80% lower &bgr;1subunit protein compared with young rats (P<0.05). Moreover, the abundance of &agr;1and &bgr;1mRNA (assessed by reverse transcriptase—polymerase chain reaction) was similar in young rats but was 2.5-fold (&agr;1) and 4.3-fold (&bgr;1) lower in old SHR compared with old WKY. In conclusion, our findings show that both aging and hypertension decrease sGC expression and its NO-dependent activation in aortic tissue. Downregulation of sGC may therefore contribute to arterial dysfunction in senescence and chronic hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

To identify the biological covariates of microalbuminuria (albuminuria ≥15 &mgr;g/min) in nondiabetic subjects, brachial blood pressure, echocardiographic left ventricular mass, and other cardiovascular and metabolic parameters were evaluated in 211 untreated males (38 normal controls, 109 uncomplicated stage 1 to 3 essential hypertensives, and 64 patients with clinically stable atherosclerotic peripheral vascular disease either with [n=44] or without [n=20] essential hypertension) with normal cardiac and renal function. Compared with normoalbuminuric subjects, microalbuminuric subjects (n=67) were characterized by higher systolic blood pressure, comparable diastolic blood pressure, and, therefore, wider pulse pressure. Greater prevalence of hypertension, peripheral vascular disease, left ventricular hypertrophy, and reduced HDL cholesterol values further distinguished microalbuminuric from normoalbuminuric subjects in univariate comparisons. The risk of microalbuminuria increased by ascending pulse pressure quintiles in age-corrected logistic regression models, in which pulse pressure was more predictive than systolic pressure and was independent of mean pressure. When microalbuminuric status was regressed against a series of dichotomous (vascular and active smoker status) and continuous (age, pulse and mean pressure, left ventricular mass index, and HDL and LDL cholesterol) variables, only pulse pressure, left ventricular mass index, and smoking status were independent predictors. The association of increased albuminuria with wider pulse pressure, a correlate of the pulsatile hemodynamic load and conduit vessel stiffness as well as an important cardiovascular risk factor, may explain why microalbuminuria predicts cardiovascular events in nondiabetic subjects. The independence from concomitant vascular disease also suggests that wider pulse pressure, rather than representing a simple marker for atherosclerotic disease, influences albuminuria directly.

ISSN:0194-911X    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Apart from ACE, various angiotensin II (Ang II)–forming serine proteinases (eg, chymase, kallikrein, and cathepsin G) are known to exist in human tissues, but their clinical significance or the regulatory mechanisms that control their activities are not well established. A recent clinical study has shown that chymase activity was significantly increased in human atherosclerotic or aneurysmal aorta. The association between vascular Ang II–forming activities (AIIFAs) in the human internal thoracic artery (ITA) and various clinical parameters was studied with the use of ITAs obtained from 32 patients who underwent coronary artery bypass graft surgery. Total and ACE- and chymase-dependent AIIFAs in homogenates of ITAs were determined. Total AIIFA was 8.67±0.86 (nmol Ang II formed · min−1· mg protein−1[U]), and ≈95% of the activities were due to chymase. Serum total cholesterol level, but no other risk factors, significantly correlated with chymase- (r=0.60,P<0.001) and ACE- (r=0.35,P<0.05) dependent AIIFAs, respectively. LDL cholesterol level was also correlated with chymase-dependent AIIFAs (r=0.47,P<0.05). Mast cells identified through the use of toluidine blue or immunohistochemical staining appeared in the adventitia but not in the intima or media of ITAs. Our results suggest that an increased plasma LDL cholesterol level may induce increased arterial chymase and ACE activity.

ISSN:0194-911X    

出版商:OVID    

年代:2000

数据来源: OVID