Abstract:
RATIONALE:Cicletanine (CIC), an anti-hypertensive compound with direct vascular and natriuretic actions, is especially effective in salt-sensitive hypertension, in which dysregulation of the sodium pump plays an important pathogenic role, and digitalis-like cardiotonic steroids contribute to increased vascular tone. The purpose of the present study was to investigate whether, and by what mechanisms, cicletanine antagonizes the vasoconstrictor effects of cardiotonic steroids in isolated human arteries. METHODS:The effects of cicletanine on vascular tone were studied in isolated, endothelium-denuded rings of 2nd-3rd-order branches of human mesenteric arteries pre-contracted with bufodienolide marinobufagenin (MBG), an Na/K-ATPase inhibitor, or endothelin-1 (ET-1). Na/K-ATPase activity was measured in sarcolemmal membranes from the mesenteric artery. Activity of rat brain protein kinase C (PKC) was measured using the PepTag phosphorylation assay. RESULTS:MBG and ET-1 both induced sustained vasoconstriction in human mesenteric artery rings, and cicletanine relaxed rings pre-contracted with either MBG (EC50 = 11 +/- 2 micromol/l) or ET-1 (EC50 = 6.4 +/- 1.1 micromol/l). Although 8-Br-cGMP (100 micromol/l) caused complete vasorelaxation of arterial rings pre-contracted with ET-1, it did not affect the MBG-induced vasoconstriction. An activator of PKC, phorbol diacetate (PDA) (50 nmol/l), attenuated CIC-induced vasorelaxation of mesenteric artery rings pre-contracted with MBG (EC50 > 100 micromol/l), but not rings pre-contracted with ET-1 (EC50 = 6.5 +/- 1.2 micromol/l). In mesenteric artery sarcolemma, 100 nmol/l MBG inhibited the Na/K-ATPase by 68 +/- 5% and cicletanine (100 micromol/l) attenuated this Na/K-ATPase inhibition by 85 +/- 6%. In the PepTag PKC assay, cicletanine produced a concentration-dependent inhibition of rat brain PKC activity (IC50 45 +/- 11 micromol/l). In the presence of 50 nmol/l PDA, 100 micromol/l cicletanine did not antagonize the Na/K-ATPase inhibition by MBG, and did not inhibit the PKC from rat brain. CONCLUSIONS:Cicletanine antagonizes vasoconstriction induced by Na/K-ATPase inhibition via a PKC-dependent mechanism that does not involve inhibition of cyclic GMP phosphodiesterase (cGMP-PDE). This mechanism of action may be relevant to the greater potency of cicletanine in salt-sensitive hypertension in which plasma levels of endogenous digitalis-like cardiotonic steroids are elevated. Our findings also suggest that PKC is an important factor for cardiotonic steroid-Na/K-ATPase interactions on the vascular tone, and is therefore a potential target for therapeutic intervention in hypertension.
journal_name
J Hypertensjournal_title
Journal of hypertensionauthors
Bagrov AY,Dmitrieva RI,Dorofeeva NA,Fedorova OV,Lopatin DA,Lakatta EG,Droy-Lefaix MTdoi
10.1097/00004872-200018020-00012subject
Has Abstractpub_date
2000-02-01 00:00:00pages
209-15issue
2eissn
0263-6352issn
1473-5598journal_volume
18pub_type
杂志文章abstract:OBJECTIVES:When assessing arterial stiffness, heart rate (HR) and blood pressure (BP) are potential confounders. It appears that the HR/BP dependences of pulse wave velocity (PWV) and distensibility are different, even though both assess arterial stiffness. This study aims to compare aortic PWV as measured using pulse ...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000002608
更新日期:2021-01-01 00:00:00
abstract::The postulated antihypertensive effect of dietary fish oil and the influence of dietary sodium on this effect were evaluated in young stroke-prone spontaneously hypertensive rats (SHRSP) by direct intra-arterial measurement of blood pressure. Weaning rats were fed synthetic diets containing olive oil or eicosapentaeno...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199107000-00009
更新日期:1991-07-01 00:00:00
abstract::Calcium blockers may reduce contractility of vascular smooth muscle as well as that of myocardial cells. Therefore, falls in both total peripheral vascular resistance (TPR) and cardiac output (CO) might be responsible for a fall in blood pressure (BP) caused by calcium blockers in essential hypertension. We have studi...
journal_title:Journal of hypertension
pub_type: 临床试验,杂志文章
doi:
更新日期:1988-02-01 00:00:00
abstract::If ambulatory blood pressure measurement is not possible because the upper-arm circumference is so great that even the largest cuff provided with the monitor will not encircle the arm, satisfactory measurements can be obtained by applying a cuff to the forearm. ...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e32834192ef
更新日期:2011-03-01 00:00:00
abstract:OBJECTIVE:We tested the reproducibility of ambulatory blood pressure (ABP), BP variability, and BP reduction in hypertensive patients. METHODS:Forty-two hypertensive patients were enrolled, and ABP monitoring (ABPM) was performed four times in each patient: twice before and twice after the treatment. Morning BP was de...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e3283378477
更新日期:2010-05-01 00:00:00
abstract:AIM:Studies addressing the association between a reduced drop of heart rate (HR) at night with subclinical organ damage and cardiovascular events in the general population are scanty. We evaluated this issue in individuals enrolled in the Pressioni Monitorate E Loro Associazioni study. METHODS:At entry, 2021 individua...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000001703
更新日期:2018-06-01 00:00:00
abstract::Several myosin isoforms are expressed in smooth muscle, based upon both heavy and light chain polymorphisms. These myosin isoenzymes reveal distinct detachment rate constants, thus regulating the responsiveness of the VSMC contractile apparatus to Ca2+, as well as its energetical and mechanical behavior. ...
journal_title:Journal of hypertension
pub_type: 杂志文章,评审
doi:10.1097/00004872-199205000-00002
更新日期:1992-05-01 00:00:00
abstract:OBJECTIVE:Circulating biomarkers of endothelial dysfunction and inflammation are elevated in late pregnancy in women with preeclampsia. We examined plasma levels of inflammatory cytokines and adhesion molecules in early pregnancy, to assess their ability to predict preeclampsia. METHODS:In a prospective longitudinal s...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e328352573b
更新日期:2012-05-01 00:00:00
abstract:OBJECTIVE:To determine whether taurine reduces blood pressure by stimulating the renal kallikrein-kinin system. METHODS:The effects of taurine on blood pressure, urinary kallikrein activity and renal kallikrein gene expression were investigated in Dahl salt-sensitive (Dahl-S) rats. The specificity of the action of tau...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:
更新日期:1994-06-01 00:00:00
abstract:OBJECTIVE:The genetic background of orthostatic hypotension, an important risk factor for future cardiovascular morbidity and mortality, was investigated. DESIGN AND METHODS:The study subjects comprised 415 community-dwelling individuals, who were free from any cardiovascular complications, aged 50 years or older (mea...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-200204000-00022
更新日期:2002-04-01 00:00:00
abstract:BACKGROUND:Little data is available concerning the prognostic implications of renal function abnormalities, their evolution over time and the effects of nifedipine on such abnormalities in patients with stable angina pectoris. METHODS:The previously published ACTION trial compared long-acting nifedipine GITS 60 mg onc...
journal_title:Journal of hypertension
pub_type: 杂志文章,随机对照试验
doi:10.1097/HJH.0b013e3281c49d93
更新日期:2007-08-01 00:00:00
abstract:OBJECTIVES:Arterial stiffness is associated with excess morbidity and mortality, independently of other cardiovascular risk factors. Age is the main determinant responsible for arterial wall changes leading to arterial stiffening. Environmental and genetic factors may however influence the magnitude of the effects of a...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-200103000-00008
更新日期:2001-03-01 00:00:00
abstract:OBJECTIVE:Low insulin sensitivity is closely related to both cardiovascular diseases and diabetes development. Still, correlates of insulin sensitivity have mainly been examined in cross-sectional studies. As far as we are aware, the longitudinal stability of insulin sensitivity in young men is largely unknown. We aime...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000000632
更新日期:2015-09-01 00:00:00
abstract:OBJECTIVES:Acute hypertensive response (AHR) in acute stroke is associated with adverse outcomes; however, the underlying pathophysiology of the association is poorly understood and its prognostic impact in ischemic stroke remains unclear. We aimed to investigate the prognostic significance of AHR in patients with isch...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000002171
更新日期:2019-12-01 00:00:00
abstract:OBJECTIVE:Disruption of vitamin D signaling in rodents causes activation of the rennin-angiotensin system (RAS) and development of hypertension. Observational studies in humans found lower circulating 25-hydroxyvitamin D [25(OH)D] is associated with increased RAS activity and blood pressure (BP). We performed the first...
journal_title:Journal of hypertension
pub_type: 杂志文章,随机对照试验
doi:10.1097/HJH.0000000000001220
更新日期:2017-04-01 00:00:00
abstract:BACKGROUND:The catalytic alpha and smaller beta subunits of the plasma membrane Na,K-ATPase occur in various molecular forms (alpha1, alpha2, alpha3, beta1 and beta2). The alpha isoforms of the enzyme have varying affinities for ouabain and exist in different tissues with particular distribution patterns. OBJECTIVE:To...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199816020-00003
更新日期:1998-02-01 00:00:00
abstract:OBJECTIVE:Molecular variants of the angiotensinogen (AGT) and the angiotensin II type 1 receptor (ATR) genes have been associated with the risk of coronary artery disease (CAD) and myocardial infarction (MI), but data so far available are conflicting. The primary object of the paper is to verify this possible associati...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-200105000-00007
更新日期:2001-05-01 00:00:00
abstract::The purpose of this study was to examine pressor responsiveness in a rabbit model with adrenal perturbation. Adrenals in rabbits were stabbed with a needle, and the rabbits were given water (adrenal-water group) or 0.9% NaCl (adrenal-salt) to drink; additional rabbits were sham-operated and given water (sham-water gro...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-198502000-00014
更新日期:1985-02-01 00:00:00
abstract:OBJECTIVES:Strong evidence has secured aging as a powerful predictor of both cardiovascular risk and endothelial dysfunction, yet specific treatment is not available. We tested the hypothesis that vascular responsiveness to flavanol-rich cocoa increases with advancing age. We have previously shown that flavanol-rich co...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/01.hjh.0000239293.40507.2a
更新日期:2006-08-01 00:00:00
abstract:OBJECTIVE:Metabolic syndrome (MetS) is associated with uncontrolled blood pressure (BP), despite use of aggressive therapy. This study was performed to assess whether the use of different classes of antihypertensive drugs might influence this association. METHODS:We evaluated risk of uncontrolled BP (BP ≥ 140/90 mmHg ...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e32834e1eda
更新日期:2012-01-01 00:00:00
abstract:OBJECTIVE:Despite the widespread use of multivitamin supplements, little is known regarding their effects on blood pressure (BP) and the development of hypertension. We, therefore, sought to prospectively investigate how multivitamin use was associated with incident hypertension among middle-aged and older women. METH...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000000973
更新日期:2016-08-01 00:00:00
abstract::The mechanisms involved in the diuretic action of the recently discovered group of atrial natriuretic peptides (ANP) are not entirely clear. To determine whether the diuresis and the changes in blood pressure produced by alpha-human ANP (alpha-hANP) involved a concomitant modification of circulating arginine-vasopress...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-198610000-00016
更新日期:1986-10-01 00:00:00
abstract:OBJECTIVE:To evaluate the wave reflection characteristics in the aortic arch and common carotid artery of ex-preterm adolescents and assess their relationship to central blood pressure in a cohort followed prospectively since birth. METHODS:Central blood pressures, pulse wave velocity, augmentation index, microvascula...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000001719
更新日期:2018-07-01 00:00:00
abstract:OBJECTIVES:To examine: (1) in how many treated hypertensive patients it was possible to discontinue drug treatment; (2) the time-course for redevelopment of hypertension after discontinuation of therapy; and (3) whether drug withdrawal was associated with an increase in left ventricular mass (LVM). DESIGN:Fifty-four m...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199206000-00012
更新日期:1992-06-01 00:00:00
abstract:OBJECTIVE:Spontaneously hypertensive rats (SHR) are sensitive to a high salt intake and we investigated the question of whether flow-induced dilation is affected by this type of diet, as flow responses are especially sensitive to small changes in extracellular sodium concentrations. METHODS:We evaluated the effects of...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199816100-00013
更新日期:1998-10-01 00:00:00
abstract::Neutrophils possess a plasma-membrane-bound reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase which catalyzes superoxide (O2-) formation and is activated by a variety of stimuli. Recently, neutrophils of patients with essential hypertension (EHT) have been reported to generate O2- at rates up to four...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199102000-00008
更新日期:1991-02-01 00:00:00
abstract:OBJECTIVE:The aim of this cross-sectional study was to investigate the association between consumption of sugar-sweetened and diet soft drinks with blood pressure (BP) in adolescents. METHODS:Fifth graders of 20 public schools were invited to participate in an intervention aimed at behavioral dietary changes and had t...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000000800
更新日期:2016-02-01 00:00:00
abstract:OBJECTIVES:Several studies have shown lower carotid-femoral pulse wave velocity (cfPWV) levels in women compared to men, a difference that could partially explain the increased longevity in women. However, these studies have been performed in industrial countries while few data are available in emerging populations. We...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e3283639460
更新日期:2013-11-01 00:00:00
abstract:OBJECTIVE:Inherited differences in renal function underlie the effect of high salt diets on blood pressure in Dahl rats. We probed the kidneys of inbred Dahl SS/Jr and SR/Jr for anonymous and candidate genes whose expression was regulated by dietary sodium. METHODS:mRNA quantitation of both candidate genes implicated ...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/01.hjh.0000133719.94075.e2
更新日期:2004-08-01 00:00:00
abstract:OBJECTIVE:The aim of the study was to examine the associations of birth outcomes and longitudinally measured fetal and infant growth patterns with retinal vessel calibers in childhood. METHODS:In a population-based prospective cohort study among 4122 children, we measured growth characteristics in second and third tri...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000000561
更新日期:2015-07-01 00:00:00