ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Increased plasma renin activity (PRA) has been associated with an increased risk of myocardial infarction (MI), whereas angiotensin-converting enzyme (ACE) inhibition appears to reduce the risk of recurrent MI in patients with left ventricular dysfunction. These observations may be partially explained by an interaction between the renin-angiotensin system (RAS) and fibrinolytic system. To test this hypothesis, we examined the effect of salt depletion on tissue-type plasminogen activator (tPA) antigen and plasminogen activator inhibitor-1 (PAI-1) activity and antigen in normotensive subjects in the presence and absence of quinapril (40 mg BID). Under low (10 mmol/d) and high (200 mmol/d) salt conditions there was significant diurnal variation in PAI-1 antigen and activity and tPA antigen. Morning (8 AM through 2 PM) PAI-1 antigen levels were significantly higher during low salt intake compared with high salt intake conditions (ANOVA, F=5.8, P=0.048). PAI-1 antigen correlated with aldosterone (r=0.56, P<10-7) during low salt intake. ACE inhibition significantly decreased 24-hour (ANOVA for 24 hours, F=6.7, P=0.04) and morning (F=24, P=0.002) PAI-1 antigen and PAI-1 activity (F=6.48, P=0.038) but did not alter tPA antigen. Thus, the mean morning PAI-1 antigen concentration was significantly higher during low salt intake than during either high salt intake or low salt intake and concomitant ACE inhibition (22.7 +/- 4.6 versus 16.1 +/- 3.3 and 16.3 +/- 3.7 ng/mL, respectively; P<0.05). This study provides evidence of a direct functional link between the RAS and fibrinolytic system in humans. The data suggest that ACE inhibition has the potential to reduce the incidence of thrombotic cardiovascular events by blunting the morning peak in PAI-1. (Hypertension. 1998;32:965-971.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

135/85 mm Hg. These data reveal that in white but not black adults, fenfluramine-induced prolactin release correlates inversely with BP and may indicate a role of central serotonergic activity in the pathogenesis of hypertension. (Hypertension. 1998;32:972-975.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The influence of intracellular administration of angiotensin II (Ang II) on the inward calcium current (ICa) was investigated in single myocytes isolated from adult rat ventricle. Comparative studies were also made in ventricular cells of Golden hamsters. The ICawas measured in single cells using the whole-cell voltage clamp configuration. The results indicated that Ang II (10-8mmol/L) dialyzed into the rat myocytes reduced the peak ICaby 35 +/- 5.5% (n=20; P<0.05). Losartan (10-7mmol/L) added to the bath did not suppress the effects of Ang II, indicating that the peptide is acting intracellularly. Moreover, the intracellular dialysis of losartan (10-6mmol/L) or [Sar1Val5Ala8] Ang II (10-6mmol/L) did not change the effect of Ang II. Stimulation of ICaby exogenous cAMP or inhibition of protein kinase C did not alter the effect of Ang II on ICa. Zaprinast (100 [micro sign]mol/L), an inhibitor of cGMP phosphodiesterase, when added to the bath solution increased appreciably the effect of Ang II on ICa(P<0.05). In ventricular myocytes of Golden hamsters, in which Ang II has a positive inotropic action, the intracellular administration of Ang II (10-8mmol/L) increased ICa0.05). The effect of the peptide was not altered by the intracellular administration of losartan (10-6mmol/L), by [Sar1Val5Ala8] Ang II (10-6mmol/L), or by the inhibitor of protein kinase A. The inhibition of protein kinase C, however, prevented the effect of Ang II I (Ca) in the hamster myocytes. The results particularly suggest that the activation of the cardiac renin-angiotensin system regulates ICaand myocardial contractility, an effect that varies with the species. (Hypertension. 1998;32:976-982.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

A wide pulse pressure (PP) is a marker of increased artery stiffness and high cardiovascular (CV) risk. To investigate the prognostic value of ambulatory PP, which is currently unknown, we studied 2010 initially untreated subjects with uncomplicated essential hypertension (mean age, 51.7 years; 52% men). All subjects underwent baseline procedures including 24-hour noninvasive ambulatory blood pressure (BP) monitoring. The mean duration of follow-up was 3.8 years (range, 0 to 11 years), and CV morbidity and mortality were the outcome measures. There were 200 major CV events (2.61 per 100 person-years), 36 of which were fatal (0.47 per 100 person-years). In the 3 tertiles of the distribution of office PP, the rate of total CV events (per 100 persons per year) was 1.38, 2.12, and 4.34, respectively, and that of fatal events was 0.12, 0.30, and 1.07 (log-rank test, both P<0.01). In the 3 tertiles of the distribution of average 24-hour PP, the rate of total CV events was 1.19, 1.81, and 4.92, and that of fatal events was 0.11, 0.17, and 1.23 (log-rank test, both P<0.01). After controlling for several independent risk markers including white coat hypertension and nondipper status, we found that ambulatory PP was associated with the biggest reduction in the -2 log likelihood statistics for CV morbidity (P<0.05 versus office PP). In each of the 3 tertiles of office PP, CV morbidity and mortality increased from the first to the third tertile of average 24-hour ambulatory PP (log-rank test, all P<0.01). Age, left ventricular hypertrophy, and nondipper status were independent predictors of CV mortality, and the further predictive effect of ambulatory PP (P<0.001) was marginally but not significantly superior to that of office PP and average 24-hour systolic BP. We conclude that ambulatory PP is a potent risk marker in essential hypertension. CV morbidity is more closely predicted by ambulatory than by office PP even after control for multiple risk factors. (Hypertension. 1998;32:983-988.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Losartan was the first available orally administered selective antagonist of the angiotensin II type 1 receptor developed for the treatment of hypertension. The Losartan Intervention For Endpoint (LIFE) Reduction in Hypertension Study is a double-blind, prospective, parallel group study designed to compare the effects of losartan with those of the beta-blocker atenolol on the reduction of cardiovascular morbidity and mortality. Patients with essential hypertension, aged between 55 and 80 years, and ECG-documented left ventricular hypertrophy (LVH) were included. Altogether, 9223 patients in Scandinavia, the United Kingdom, and the United States were randomized from June 1995 through April 1997, and 9194 remain after exclusion of a study center at which irregularities were discovered. This population of hypertensives (mean systolic/diastolic blood pressure, 174.4/97.8 mm Hg) with LVH comprises women (54.1%) and men, mostly retired from active work (mean age, 66.9 years), with a high prevalence of overweight (mean body mass index, 28.0 kg/m2), diabetes mellitus (12.3%), lipid disorders (18.0%), and symptoms or signs of coronary heart disease (15.1%). There were fewer current smokers (<17%) than in the general population, and [almost equal to]7% were nonwhite. Almost 30% of participants had been untreated for at least 6 months when screened for the study. Only 1557 persons who entered the placebo run-in period of 14 days were excluded, predominantly because of sitting blood pressures above or below the predetermined range of 160-200/95-115 mm Hg and ECG-LVH criteria not met. By application of simple 12-lead ECG criteria for LVH (Cornell voltage QRS duration product formula plus Sokolow-Lyon voltage read by a core laboratory), hypertensive patients with LVH with an average 5-year coronary heart disease risk of 22.3% according to the Framingham score were identified. This population is now being treated (goal, <140/90 mm Hg) in adherence with the protocol for at least 4 years after final enrollment (ie, through April 2001) and until at least 1040 patients suffer myocardial infarction, stroke, or cardiovascular death. (Hypertension. 1998;32:989-997.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

or=to90 mm Hg or undergoing drug therapy); 12% had isolated systolic hypertension, and 8.7% had isolated diastolic hypertension. Pulse pressure was 48.7 mm Hg. Heart rate was 81.4 bpm in untreated hypertensives and 78.9 bpm in normotensives (P<0.05). A substantial proportion of the community burden of blood pressure was attributable to stage 1 (28.3% of subjects), the most frequent category of hypertension, and to the high-normal blood pressure group (17% of subjects). A percentage breakdown showed that among hypertensives, 44.5% were aware of their condition; of these, 71.9% were undergoing drug therapy, and of those being treated, only 15.5% were controlled (5% of hypertensives). Not only are these figures consistent with the fact that Spain has a higher cerebrovascular mortality than other countries such as the United States, but they represent a great potential for improvement, particularly among those groups registering relatively worse data (younger men, rural residents, and unskilled professionals). A decrease of only 1 to 4 mm Hg in average blood pressure could reduce the prevalence of hypertension in Spain by 12.4% to 15.4%. (Hypertension. 1998;32:998-1002.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

8-fold of that seen in control cells at 5 minutes. This was blocked by catalase, which suggests that H2O2was the principal ROS. The oleic acid-induced increases in H2O2were blocked when PKC was inhibited with the use of bisindolylmaleimide and when PKC activity was downregulated by exposing RASMCs to phorbol 12-myristate 13-acetate for 24 hours. Stearic and elaidic acids, which are weak PKC activators, did not significantly increase H2O2production. The increase of H2O2in response to oleic acid was inhibited by the antioxidant N-acetylcysteine. N-Acetylcysteine also completely blocked ERK activation and the increase of thymidine incorporation in response to oleic acid. The data suggest that generation of H2O2in RASMCs exposed to oleic acid is PKC dependent. Moreover, H2O2production emerges as a critical intermediary event in the oleic acid-mediated mitogenic signaling pathway between the activation of PKC and ERK. These observations raise the possibility that the elevated plasma nonesterified fatty acids, including oleic acid, in obese hypertensive patients contribute to vascular growth and remodeling by a PKC-dependent mechanism to generate ROS that subsequently activate ERK. (Hypertension. 1998;32:1003-1010.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

An imbalance between nitric oxide (NO) and superoxide is importantly involved in the pathogenesis of vascular disease. Inflammatory stimuli and risk factors contribute to these alterations. Calcium antagonists and angiotensin-converting enzyme inhibitors are commonly used cardiovascular drugs. To clarify the effect of felodipine and ramiprilat on the balance of these free radicals, we stimulated human aortic smooth muscle cells (HASCs) with cytokines (human interleukin-1 beta, tumor necrosis factor-alpha, lipopolysaccharide, and/or interferon-gamma) or high glucose in the presence and absence of these compounds. Felodipine, but not ramiprilat, concentration-dependently inhibited cytokine-induced NO production and NO synthase (NOS) mRNA induction. The antioxidant N-acetylcysteine also inhibited cytokine-induced NO production and induction of inducible NOS mRNA. Moreover, felodipine inhibited cytokine-induced superoxide production both in the presence and absence of an NOS inhibitor, suggesting that it acted as a superoxide scavenger and not as an inhibitor of inducible NOS induction. High glucose treatment (22 mmol/L for 48 hours) also significantly increased superoxide production in HASCs, and this increase was inhibited in a concentration-dependent manner by felodipine but not by ramiprilat. These results suggest that felodipine may exert vascular protective effects by suppressing free radical generation in human smooth muscle cells during activation of inflammatory mechanisms and diabetic conditions. (Hypertension. 1998;32:1011-1015.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID