ISSN:0194-911X    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The Family Blood Pressure Program (FBPP) consists of 4 independently established multicenter networks of investigators who have complementary approaches to the genetics of blood pressure levels and hypertension. The program has recruited participants from the African American, Mexican American, Asian, and non-Hispanic white populations. Each network utilized study designs, laboratory measurements, and analytic methods that made efficient use of the unique characteristics of their populations and the investigators’ expertise. The individual networks subsequently unified core study components into a single cohesive program. The unified FBPP includes (1) standardized clinic and laboratory protocols for core variables to facilitate direct comparison of results among networks, (2) coordination among laboratories to avoid unnecessary duplication of effort, (3) utilization of a single laboratory for genome-wide marker typing, and (4) a pooled data set containing phenotype and genotype information from >11 000 individuals.

ISSN:0194-911X    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Arterial stiffness may predict coronary heart disease beyond classic risk factors. In a longitudinal study, we assessed the predictive value of arterial stiffness on coronary heart disease in patients with essential hypertension and without known clinical cardiovascular disease. Aortic stiffness was determined from carotid-femoral pulse wave velocity at baseline in 1045 hypertensives. The risk assessment of coronary heart disease was made by calculating the Framingham risk score according to the categories of gender, age, blood pressure, cholesterol, diabetes, and smoking. Mean age at entry was 51 years, and mean follow-up was 5.7 years. Coronary events (fatal and nonfatal myocardial infarction, coronary revascularization, and angina pectoris) and all cardiovascular events served as outcome variables in Cox proportional-hazard regression models. Fifty-three coronary events and 97 total cardiovascular events occurred. In univariate analysis, the relative risk of follow-up coronary event or any cardiovascular event increased with increasing level of pulse wave velocity; for 1 SD, ie, 3.5 m/s, relatives risks were 1.42 (95% confidence interval [CI], 1.10 to 1.82;P<0.01) and 1.41 (95% CI, 1.17 to 1.70;P<0.001), respectively. Framingham score significantly predicted the occurrence of coronary and all cardiovascular events in this population (P<0.01 andP<0.0001, respectively). In multivariate analysis, pulse wave velocity remained significantly associated with the occurrence of coronary event after adjustment either of Framingham score (for 3.5 m/s: relative risk, 1.34; 95% CI, 1.01 to 1.79;P=0.039) or classic risk factors (for 3.5 m/s: relative risk, 1.39; 95% CI, 1.08 to 1.79;P=0.01). Parallel results were observed for all cardiovascular events. This study provides the first direct evidence in a longitudinal study that aortic stiffness is an independent predictor of primary coronary events in patients with essential hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Although conduit arteries develop hypertrophy after chronic NO synthesis blockade, resistance arteries remodel without hypertrophy under the same conditions. Similar findings have been described in essential hypertension. We postulated that this regional difference may be related to a heterogeneous effect of endogenous NO on proliferation along the vascular tree. Newly synthesized proteins were radiolabeled in vivo with [3H]l-leucine in basal conditions and during NO synthase inhibition, with or without PD98059 (inhibitor of the extracellular signal–regulated kinases [ERK] 1/2). Blocking the generation of NO by 3 different l-arginine analogues increased protein synthesis by an average of 75% in the aorta, in association with enhanced ERK 1/2 phosphorylation. PD98059 significantly reduced l-arginine analogue–induced protein synthesis and ERK 1/2 phosphorylation, confirming the involvement of ERK 1/2 as an important signaling element. In small arteries, l-arginine analogues did not influence the extent of protein synthesis, although phosphorylation of ERK 1/2 was also enhanced. To determine the role of NO in a condition of enhanced protein synthesis, angiotensin II was infused for 24 hours. Angiotensin II augmented protein synthesis in mesenteric arteries and the aorta, and was additive to NO synthase blockade in the aorta. In conclusion, endogenous NO exerts a tonic inhibitory influence on aortic growth, with limited impact on small arteries in basal and hypertrophic conditions. This heterogeneous role of NO on vascular growth may explain the heterogeneity of vascular remodeling observed in essential hypertension, a condition associated with endothelial dysfunction.

ISSN:0194-911X    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Nonenzymatic glycation is increased in diabetes. The role of advanced glycation end products has been implicated in many of the complications of diabetes, whereas the effects of early-glycation Amadori-modified proteins on vascular cells alone are poorly defined. In the present study, we show that glycated serum albumin (GSA) induces a parallel activation of the redox-responsive transcription factors (nuclear factor &kgr;B) and AP-1 and increases activity of mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK), and p38 MAPK in vascular smooth muscle cells (VSMCs). GSA increased expression of early response genes, c-fosand c-jun, and inflammatory genes, monocyte chemoattractant peptide (MCP-1), and interleukin (IL)-6. These effects were comparable to bacterial lipopolysaccharide, tumor necrosis factor-&agr;a, (TNF-&agr;a), IL-1&agr;b, angiotensin II, epidermal growth factor, and the phorbol ester PMA. One of signaling pathways by which GSA activates VSMCs appears to be via nuclear factor &kgr;B activation, leading to induction of MCP-1 and IL-6 gene expression, comparable to the effects of lipopolysaccharide, TNF-&agr;a, and IL-1&agr;b. Another signaling cascade by which GSA activates VSMCs is the ERK→c-Fos→AP-1 pathway, which may lead to stimulation of cell proliferation and migration. These effects are comparable to the effects of angiotensin II, epidermal growth factor, and PMA. Incubation of VSMCs with the antioxidantN-acetylcysteine suppressed GSA-elicited mRNA induction of MCP-1 and IL-6. Inhibition of p38 MAPK but not ERK caused attenuation of MCP-1 and IL-6 mRNA induction. Finally, GSA caused a significant stimulation of VSMC growth and migration. These findings suggest that GSA may play a role in diabetic atherogenesis by activating VSMCs, leading to induction of inflammatory mediators in the vessel wall, as well as proliferation and migration of VSMCs.

ISSN:0194-911X    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Bradykinin evokes endothelium-dependent relaxation in some vascular beds; on the other hand, the possibility has been demonstrated that in certain organs, such as the adrenal medulla or atria, bradykinin may enhance transmitter release from the sympathetic nerves. We hypothesized that bradykinin may also enhance postganglionic sympathetic neurotransmission in blood vessels. To test this hypothesis, we recorded excitatory junction potentials (EJPs), a measure of sympathetic purinergic neurotransmission, in rat mesenteric resistance arteries with a conventional microelectrode technique. EJPs were elicited by repetitive perivascular nerve stimulation (1 Hz, 20 to 50 V, 30 to 60 &mgr;s, 11 pulses). In this preparation, bradykinin (10−7or 10−6mol/L) significantly enhanced the amplitude of EJPs without altering the resting membrane potential. This effect of bradykinin was blocked by Hoe 140, a bradykinin B2 receptor antagonist, but not by des-Arg9,[Leu8]-bradykinin, a bradykinin B1 receptor antagonist. The cyclooxygenase inhibitor indomethacin or NO synthase inhibitorNG-nitro-l-arginine did not alter the effect of bradykinin. Captopril, an ACE inhibitor, but not candesartan, an angiotensin II type 1 receptor antagonist, enhanced the action of a low concentration (10−8mol/L) of bradykinin on EJPs. These findings suggest that in rat mesenteric resistance arteries, bradykinin enhances sympathetic purinergic neurotransmission, presumably through presynaptic bradykinin B2 receptors. The clinical relevance of the present findings remains unclear; however, the fact that the ACE inhibitor, but not the angiotensin II type 1 receptor antagonist, enhanced the action of bradykinin on sympathetic neurotransmission may warrant further investigation.

ISSN:0194-911X    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Hyperinsulinemia is a risk factor for hypertension and arteriosclerosis. The mechanism by which it contributes to disease progression is not known. The present study examines the effects of insulin on endothelium-derived relaxing factors. Segments of rat mesenteric arterioles and aorta were set up for isometric recordings. The effect of insulin (1 mU/mL) on acetylcholine responses was examined with and without nitro-l-arginine, indomethacin, KCl (40 mmol/L), and apamin+charybdotoxin. Incubation with insulin (maximum response to acetylcholine 90.9±8.7% versus 90.7±4.5% for before versus after insulin, respectively), nitro-l-arginine, indomethacin, or high K+alone had no effect on these responses in mesenteric arterioles. Apamin+charybdotoxin significantly blunted responses to acetylcholine. When coincubated with nitro-l-arginine but not with indomethacin or high K+, insulin blunted the maximum response to acetylcholine (from 84.8±8.2% to 40.7±10.2% for before versus after insulin, respectively;P<0.01). When coincubated with apamin+charybdotoxin, insulin had no further effect. Coadministration of indomethacin with nitro-l-arginine had no greater effect than did nitro-l-arginine alone. The addition of insulin, together with nitro-l-arginine and indomethacin, significantly decreased the maximal response to acetylcholine from 96.6±5.3% to 52.9±10.8% (P<0.01). In the aorta, nitro-l-arginine abolished acetylcholine responses. Coadministration with insulin had no further effect. We conclude that insulin attenuates acetylcholine responses mediated by endothelium-derived hyperpolarizing factor in small but not large arteries. This effect of insulin is apparent only when NO is blocked and may be important in the development of hypertension or arteriosclerosis when reduced NO function has been reported.

ISSN:0194-911X    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Accumulating evidence suggests that estrogen exerts cardioprotective effects and protects against neointima formation in response to vascular injury in vivo, whereas angiotensin (Ang) II stimulation via the Ang II type 1 (AT1) receptor exaggerates vascular injury. We postulate that estrogen treatment antagonizes the AT1receptor-mediated growth-promoting effects in vascular smooth muscle cells (VSMCs). The present in vitro study was designed to explore this possibility and to establish the cellular mechanism whereby estrogen attenuates the growth of VSMCs. Primary cultures of VSMCs derived from male adult Sprague-Dawley rats express exclusively AT1receptors. Treatment with Ang II enhanced proliferation of VSMC and c-fosexpression, whereas 17&bgr;-estradiol (E2) attenuated these vasotrophic effects of Ang II. We also demonstrated that E2 attenuated AT1receptor-mediated extracellular signal-regulated kinase activation and that this effect of E2 was restored by pretreatment with vanadate or okadaic acid. Moreover, we demonstrated that E2 enhanced SHP-1 activity, rapidly reaching a peak after 3 minutes of E2 stimulation, whereas E2 transactivated mitogen-activated protein kinase phosphatase-1 expression, showing a peak after 60 minutes of E2 treatment. SHP-1 activation was not influenced by actinomycin D treatment, whereas E2-mediated mitogen-activated protein kinase phosphatase-1 expression was attenuated. Taken together, our results suggest a novel mechanism of vasoprotection by which estrogen antagonizes the effect of the AT1receptor via the activation and induction of phosphatases through nongenomic as well as genomic signaling.

ISSN:0194-911X    

出版商:OVID    

年代:2002

数据来源: OVID