Abstract:
:The aim of this study was to examine the effects of long-term continuous intracerebroventricular (icv) infusion of metformin on blood pressure (BP) in spontaneously hypertensive rats (SHR). To accelerate the development of hypertension, SHR were fed a 8% NaCl diet during the 3-week study period. Metformin was given in the following doses: 0 (isotonic saline; n = 7), 25 (n = 8), 50 (n = 6), 100 (n = 6), and 200 microg/day icv (n = 5). Mean arterial pressure (MAP) and heart rate (HR) were measured by radiotelemetry, and as a measure of the contribution of sympathetic nerve activity to BP, the decrease in MAP in response to ganglionic blockade with hexamethonium, 30 mg/kg iv, was determined once weekly. In vehicle treated rats, MAP increased by 27+/-4 mm Hg, whereas in rats treated with a low dose of metformin (25 microg/day), MAP increased only by 7+/-3 mm Hg (P < .01). The hypotensive response to hexamethonium was attenuated by all doses of metformin suggesting that chronic icv metformin decreased central sympathetic outflow. The highest doses of metformin (100 and 200 microg/day) also prevented development of hypertension, but these doses were highly neurotoxic as demonstrated by histologic evaluation post mortem. Fast-Fourier transformation of MAP revealed increased variability within the 0.15 to 0.6 Hz frequency range in rats treated with neurotoxic doses of metformin, suggesting impaired sympathetic control of BP in these animals. In conclusion, long-term icv infusion with apparently nontoxic doses of metformin attenuates hypertension and decreases the hypotensive responses to ganglionic blockade in SHR, suggesting a centrally elicited sympathoinhibitory action.
journal_name
Am J Hypertensjournal_title
American journal of hypertensionauthors
Petersen JS,Andersen D,Muntzel MS,Diemer NH,Holstein-Rathlou NHdoi
10.1016/s0895-7061(01)02220-8subject
Has Abstractpub_date
2001-11-01 00:00:00pages
1116-22issue
11 Pt 1eissn
0895-7061issn
1941-7225pii
S0895-7061(01)02220-8journal_volume
14pub_type
杂志文章abstract:BACKGROUND:The polymorphism of several candidate genes has been studied in relation to essential hypertension and cardiovascular complications. Target organ damage in essential hypertension is a complex disorder influenced by multiple genetic and environmental factors. The possible contribution of endothelin gene varia...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/s0895-7061(01)02162-8
更新日期:2001-08-01 00:00:00
abstract:BACKGROUND:Morning blood pressure (BP) surge seems to be a risk factor for cardiovascular events. Although physical activity after arising significantly affects morning BP surge, it has remained unclear whether morning BP surge after controlling for physical activity (morning BP reactivity) is associated with target or...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/j.amjhyper.2005.06.015
更新日期:2005-12-01 00:00:00
abstract:BACKGROUND:Functional status may be useful for identifying older adults who benefit from lower blood pressure. We examined whether functional status modifies the effect of antihypertensive treatment among older adults. METHODS:Post hoc analyses of the Systolic Hypertension in the Elderly Program (SHEP), a randomized t...
journal_title:American journal of hypertension
pub_type: 杂志文章,随机对照试验
doi:10.1093/ajh/hpv177
更新日期:2016-06-01 00:00:00
abstract::The effects of dietary Na+ on 5 alpha- and 5 beta-reductase pathways of aldosterone metabolism in the liver were studied in male rats maintained on low, control, and high Na+ diets. A high Na+ diet caused significant increases in the synthesis of 5 beta-reduced metabolites, primarily 3 alpha, 5 beta-tetrahydroaldoster...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/1.3.272
更新日期:1988-07-01 00:00:00
abstract:BACKGROUND:Angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers (CCBs) increase arterial compliance and decrease left ventricular mass in hypertensive patients. This study examined whether combined therapy has greater arterial and cardiac effects than doubled doses of the individual drugs. METHO...
journal_title:American journal of hypertension
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/j.amjhyper.2003.08.002
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND:It is known that essential hypertension may be implicated in the development of cognitive impairment that is associated to microvascular disease of the brain. It has been hypothesized that increased arterial stiffness of the large arteries may lead to microvascular changes due to increased pulsatile flow. Ou...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1038/ajh.2009.35
更新日期:2009-05-01 00:00:00
abstract:BACKGROUND:Left ventricular (LV) hypertrophy and impaired diastolic function may occur early in systemic hypertension, but longitudinal studies are missing. METHODS:We performed an echocardiographic follow-up study in young initially normotensive male offspring of hypertensive (OHyp) (n = 25) and normotensive (ONorm) ...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/s0895-7061(00)01245-0
更新日期:2001-02-01 00:00:00
abstract::This study was performed to investigate the role of endogenous epinephrine in the regulation of vascular tone in hypertension. The release of endogenous epinephrine and norepinephrine from the vascular adrenergic neurons by periarterial nerve stimulation was examined in spontaneously hypertensive rats (SHR) and age-ma...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/3.1.52
更新日期:1990-01-01 00:00:00
abstract::To clarify the function of polymorphonuclear leukocytes (PMN) in spontaneously hypertensive rats (SHR) and the effect of beraprost sodium (BS) on these functions, we examined superoxide anion (O2-) production and adherent activity by PMN, as well as modification of these functions by BS ex vivo and in vitro. In study ...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/s0895-7061(01)01309-7
更新日期:2001-07-01 00:00:00
abstract:BACKGROUND:Pre-eclampsia (PE) is characterized by hypertension and proteinuria, and complicates from 3%-10% of all pregnancies. The hemodynamic pathophysiology of the heart and systemic arteries in pre-eclamptic patients has not been well described. We therefore performed a comprehensive comparison of the systemic arte...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/hps067
更新日期:2013-04-01 00:00:00
abstract::Despite advances in the availability and quality of antihypertensive medications and the institution of national programs to educate people about the seriousness of hypertension, much remains to be done. The percentages of people who are aware of their disease, are being treated for it, and are achieving adequate cont...
journal_title:American journal of hypertension
pub_type: 杂志文章,评审
doi:10.1016/s0895-7061(00)00273-9
更新日期:2000-05-01 00:00:00
abstract:BACKGROUND:Aim of this study was to evaluate the effect of the telmisartan-amlodipine combination at different doses on urinary albumin excretion rate (UAER) in hypertensive diabetic patients with microalbuminuria. METHODS:After a 2-week placebo period, 300 hypertensive patients with type 2 diabetes and microalbuminur...
journal_title:American journal of hypertension
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.amjhyper.2006.10.002
更新日期:2007-04-01 00:00:00
abstract:BACKGROUND:Renal tubulointerstitial infiltration of activated T cells and macrophages is invariably present and plays a role in elevation of arterial pressure in nearly all animal models of hypertension (HTN). The role, if any, of elevated renal arterial pressure in the pathogenesis of this inflammatory process is unce...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/j.amjhyper.2005.05.034
更新日期:2005-11-01 00:00:00
abstract::Components of the kallikrein kinin system have been associated with the pathophysiology of hypertension in animal and human studies. In this study, we examined the distribution of four different polymorphisms of the kinin B1 and B2 receptor genes in a population of 120 normotensive and 77 hypertensive African-American...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/s0895-7061(00)01215-2
更新日期:2000-12-01 00:00:00
abstract:BACKGROUND:Liddle's syndrome (LS) is a monogenic form of hypertension simulating a mineralocorticoid excess, and is currently suspected in young hypokalemic hypertensives. The aims of the study were: (i) to evaluate the clinical phenotype of LS in a newly identified Italian family of Sicilian origin carrying a gain-of-...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1038/ajh.2011.76
更新日期:2011-08-01 00:00:00
abstract::The "totality" of hypertension clinical trial endpoint data has shown that the absolute benefit of pharmacological blood pressure (BP) lowering is directly related to the BP level and baseline cardiovascular risk, albeit with attenuation of the relative risk reduction per unit of BP lowering in patients with diabetes ...
journal_title:American journal of hypertension
pub_type: 杂志文章,评审
doi:10.1093/ajh/hpw087
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Carvedilol is known to be an adrenoreceptor blocker and free radical scavenger, used in hypertension and cardiac failure. However, its therapeutic actions cannot be fully explained by these mechanisms. In these studies, we tested the hypothesis that carvedilol action is associated with the synthesis/release ...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/j.amjhyper.2005.11.011
更新日期:2006-04-01 00:00:00
abstract::The aim of this study was to investigate the effects of dietary calcium and sodium on blood pressure (BP) in normotensive rats (Wistar, WKY), spontaneously hypertensive rats (SHR) and Dahl rats and on calmodulin (CaM) activator, a newly-discovered hydrophobic compound that increases CaM activity in SHR and spontaneous...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/3.8.210
更新日期:1990-08-01 00:00:00
abstract:BACKGROUND:We hypothesized that high-dose active vitamin D therapy in the form of alphacalcidol (α-calcidol), used to treat secondary hyperparathyroidism in chronic kidney disease, could lead to vascular calcification and accelerated progression of aortic stiffness. METHODS:We conducted an observational study in 85 pa...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/hpu057
更新日期:2014-11-01 00:00:00
abstract::There is considerable evidence that activation of the sympathetic nervous system plays an important role in the pathogenesis of several cardiovascular diseases, including hypertension. However, the mechanisms that account for sympathetic activation and the precise mechanisms that mediate neurally induced hypertension ...
journal_title:American journal of hypertension
pub_type: 杂志文章,评审
doi:10.1016/s0895-7061(01)02082-9
更新日期:2001-06-01 00:00:00
abstract:BACKGROUND:Type B acute aortic dissection (AAD) carries a high short- and midterm mortality rate; however, knowledge related to long-term outcome is largely incomplete. The objective of this study was to identify long-term predictors including antihypertensive medications in type B AAD. METHODS:We conducted a clinical...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1038/ajh.2009.5
更新日期:2009-04-01 00:00:00
abstract::Although the most direct way to interfere with the renin-angiotensin system (RAS) is at the level of the angiotensin II (AII) receptor, the currently available AII receptor antagonists are peptides still retaining significant agonistic properties with the obvious drawbacks of limited stability and lack of oral activit...
journal_title:American journal of hypertension
pub_type: 杂志文章,评审
doi:10.1093/ajh/3.8.599
更新日期:1990-08-01 00:00:00
abstract:BACKGROUND:Hypertension is the most prevalent chronic disease worldwide. Lifestyle behaviors for its prevention and control are recommended within worldwide guidelines. Nevertheless, their combined relationship with blood pressure (BP) level, particularly in the general population, would need more investigations. Our a...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/hpu164
更新日期:2015-03-01 00:00:00
abstract::Recent findings related to the renin-angiotensin system have provided a more elaborated understanding of the pathophysiology of hypertension and kidney diseases. These findings have led to unique concepts and issues regarding the intrarenal renin-angiotensin system. Angiotensinogen is the only known substrate for reni...
journal_title:American journal of hypertension
pub_type:
doi:10.1016/j.amjhyper.2005.11.014
更新日期:2006-05-01 00:00:00
abstract:BACKGROUND:We compared the cost-effectiveness of hypertension treatment in non-Hispanic blacks and non-Hispanic whites according to 2014 US hypertension treatment guidelines. METHODS:The cardiovascular disease (CVD) policy model simulated CVD events, quality-adjusted life years (QALYs), and treatment costs in 35- to 7...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/hpw047
更新日期:2016-10-01 00:00:00
abstract::The levels and molecular form of atrial natriuretic peptide-like immunoreactivity (ANP-LI) in human atrial tissue were investigated. The levels of right atrial ANP-LI were significantly higher in mitral disease than in other cardiac or noncardiac diseases. The increased ANP-LI was mainly accounted for by an increase i...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/3.2.105
更新日期:1990-02-01 00:00:00
abstract::Arterial hypertension is a powerful risk factor for cardiovascular disease, but the ability to use blood pressure measurements to predict complications in individual patients or small groups is limited. One possible approach to identifying hypertensive patients at high risk is based on the observation that the presenc...
journal_title:American journal of hypertension
pub_type: 杂志文章,评审
doi:10.1093/ajh/2.8.650
更新日期:1989-08-01 00:00:00
abstract:BACKGROUND:Although several characteristics of aortic function, which are largely determined by age, predict outcomes beyond brachial blood pressure (BP), the extent to which brachial BP control accounts for age-related variations in aortic function is uncertain. We aimed to determine the extent to which brachial BP co...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/hpv140
更新日期:2016-05-01 00:00:00
abstract::Concentrations of sodium-transport inhibitors (STI) which block the sodium-potassium-ATPase pump are increased in the plasma and urine of volume-expanded and low-renin hypertensive humans and animals. To evaluate the physiologic relevance of STI to blood-pressure-raising mechanisms, we have examined the in vitro prope...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/2.10.754
更新日期:1989-10-01 00:00:00
abstract:BACKGROUND:Left ventricular (LV) concentric geometry and hypertrophy, depressed wall mechanics, and abnormal diastolic properties have been described in the diabetic heart. However, the cardiac response to dynamic exercise in diabetic patients remains controversial. The present study assessed strain rate (SR) imaging d...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/j.amjhyper.2006.12.009
更新日期:2007-05-01 00:00:00