Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activation of the RAAS has been linked with an increased risk of myocardial infarction and stroke,(1,2,37,38) and recently these beneficial effects have, in part, been attributed to the effects of the RAAS on the fibrinolytic system. Indeed, ACE seems to occupy a central position in modulating the fibrinolytic balance, where an angiotensin II-mediated increase of PAI-1 plays a major role. By contrast, the effect on bradykinin stimulated t-PA release may be of lesser importance, although the data are conflicting. Importantly, the impact of the RAAS on the fibrinolytic balance may also contribute to the favourable effects of ACE inhibition and AT1-receptor antagonists on cardiovascular events, particularly when considering the activation of the RAAS in hypertension and heart failure. More work is clearly required in this area to elucidate potential therapeutic targets.
 ...
PMID:The renin-angiotensin-aldosterone system and fibrinolysis. 1188 Oct 31

Prostacyclin is a powerful vasodilator that is released from vascular endothelial cells. Previous studies in our laboratory have indicated that arachidonic acid metabolites from venous endothelium play an important role in the dilation of adjacent arterioles during muscle stimulation. Furthermore, recent studies have suggested that ATP released from red blood cells during hypoxia stimulates dilation of arterioles. We tested the hypothesis that an ATP-induced increase in intracellular Ca(2+) in venous endothelium promotes prostacyclin synthesis. Small branches of femoral veins were isolated from male golden hamsters, placed in a 1 mL bath, and cannulated for perfusion with 3-(N-morpholino) propanesulfonic acid (MOPS)-buffered physiological salt solution at 37 degrees C. Prostacyclin synthesis was determined by enzyme immunoassay of bath solution. Perfusion of veins with ATP increased prostacyclin synthesis from 50 +/- 5 to 627 +/- 46 pg/mL (n=49). ATP-induced prostacyclin synthesis was inhibited by removal of extracellular Ca(2+), chelation of intracellular Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) (10 micromol/L for 10 minutes), and preincubation with cytosolic phospholipase A(2) (PLA(2)) inhibitors, AACOCF(3), and bromoenol lactone. Changes in intracellular Ca(2+) in cultured human venous endothelial cells were assessed by fura-2 spectrofluorometry. ATP induced a transient Ca(2+) peak within seconds, and the subsequent Ca(2+) plateau was abolished by removal of extracellular Ca(2+). An increase in prostacyclin synthesis was detected in these cells 2 minutes after application of ATP. These findings suggest that the ATP-induced increase in intracellular Ca(2+) stimulates prostacyclin synthesis in venous endothelial cells.
Hypertension 2002 Feb
PMID:Calcium-dependent synthesis of prostacyclin in ATP-stimulated venous endothelial cells. 1188 12

We have reported that norepinephrine (NE) and angiotensin II (Ang II) increase CaM kinase II activity, which, in turn, activates cytosolic phospholipase A(2) (PLA(2)) and releases arachidonic acid. The products of arachidonic acid generated via cytochrome P-450 and lipoxygenase contribute to the development of hypertension and vascular smooth muscle cell (VSMC) hyperplasia. The purpose of this study was to investigate whether CaM kinase II contributes to VSMC proliferation elicited by NE and Ang II and to hypertension induced by Ang II. NE (1 micromol/L) and Ang II (1 micromol/L) increased proliferation of rabbit aortic VSMC as measured by increased [(3)H]-thymidine incorporation; this effect of NE and Ang II was attenuated 88 +/- 10% and 64 +/- 11% by the CaM kinase II inhibitor KN-93, respectively. Infusion of Ang II with miniosmotic pumps (350 ng/min for 6 days) in rats elevated mean arterial pressure (MABP), which was reduced by simultaneous infusion of KN-93 (578 ng/min, for 6 days) (Ang II alone: MABP =174 +/- 3 mm Hg, n=12 versus Ang II + KN-93: MABP 123 +/- 5 mm Hg, n=4, P<0.05). Administration of KN-93 as a single bolus injection (16 mg/Kg), but not its vehicle, in Ang II--infused hypertensive animals also decreased MABP from 179 +/- 9 mm Hg to 109 +/- 6 mm Hg (n=5, P<0.05). CaM kinase II activity was increased in the kidney of Ang II--infused hypertensive animals compared with normotensive controls. Treatment with KN-93 reduced CaM kinase II activity and ameliorated the intravascular injury in the kidneys of Ang II--infused hypertensive rats. Our data indicate that CaM kinase activation represents an important component of the mechanism(s) initiating VSMC proliferation and the development and maintenance of Ang II--induced hypertension in rat.
Hypertension 2002 Feb
PMID:Functional significance of activation of calcium/calmodulin-dependent protein kinase II in angiotensin II--induced vascular hyperplasia and hypertension. 1188 35

Advances in neurologic therapeutics and intensive care medicine have expanded the arsenal of treatments available for the critical care of ischemic stroke. Several agents are available for acute reperfusion of the ischemic brain. These include intravenous recombinant tissue-plasminogen activator (rtPA), which is effective in a 3-hour time window, and intra-arterial thrombolytics, which may be effective within 6 hours. In addition, newer agents such as Ancrod and abciximab may be effective within the acute time period. Efforts to prevent secondary brain injury in critically ill patients with stroke often include prevention and reduction of fever, induced hypertension, and mechanical ventilation. Finally, death due to severe brain edema after massive hemispheric infarction can often be prevented with surgical or medical intervention. Unfortunately, there is a critical lack of well-designed clinical studies to guide the clinician in the use of these interventions. In addition, there is concern that some of these interventions may preserve life at the cost of quality of life. This article reviews the evidence behind these approaches to the critical care of ischemic stroke.
 ...
PMID:Critical care of acute ischemic stroke. 1189 73

Diabetes mellitus (DM) is accompanied by several cardiovascular complications such as coronary artery disease, atherosclerosis, hypertension, cerebral and myocardial infarction, etc. DM induces the alteration of platelet functions including activation, hyperaggregation, adhesiveness, and formation of thrombi. Release of AA from phospholipids of the PM, synthesis of TxA(2),PGE(2), activity of PLA(2), and PLC are increased in the platelets of the DM patients. Stimulation of PLA(2) activity and accumulation of bioactive metabolites such as AA, its oxygenated derivatives, prostaglandins and PAF can evoke glucose production, also. In this study we explored the effect of the 1,4-dihydropyridine compound cerebrocrast at a low concentration (10(-6)-10(-8)M) on the level of intracellular calcium in unstimulated human platelets and those stimulated with thrombin as well as release of [(3)H] AA from phospholipids of platelet PM. Cerebrocrast at a concentration of 10(-6) M decreased the basal level of intracellular calcium concentration (platelets were loaded with Fura-2) in unstimulated as well as in thrombin stimulated platelets. Cerebrocrast at concentrations of 10(-6), 10(-7), 10(-8) M inhibited release of [(3)H] AA from phospholipids of platelet PM. We conclude that blockade of human platelet activation with cerebrocrast can prevent aggregation, adhesion and formation of thrombi. The inhibition of [(3)H] AA release from phospholipids of platelet PM can prevent formation of eicosanoids such as TxA(2), PGG(2), and PGH(2) plus AA oxygenated derivatives. These effects of cerebrocrast are very significant in the treatment of DM-evoked cardiovascular complications.
 ...
PMID:Effect of cerebrocrast on the function of human platelets and release of the arachidonic acid from plasma membrane. 1197 14

The study was carried out in a group of 285 children and adolescents aged 4-20 yrs. Children were divided according to their main disease: group with obesity, obesity and coexisting hypertension, hypertension and diabetes. Each group was divided into children with positive or negative family history of cardiovascular diseases. We assessed routine lipid parameters, body mass index and new atherosclerosis risk factors: lipoprotein (a), apolipoproteins A-I and B, homocysteine, fibrinogen, t-PA and PAI-1. Positive family history of cardiovascular diseases was found in 28% families, and in 8% families it was premature cardiovascular disease. In 48% children we found hypertension in family. Children with positive family history had significantly higher body mass index (25.4 vs 23.8 kg/m2). In the group with obesity and hypertension we found significantly higher cholesterol (182 vs 160 mg/dl) and LDL-cholesterol level (114 vs 93 mg/dl). Lipoprotein(a) level was significantly higher in children with positive family history (38 vs 28 mg/dl). Significant differencies were also found in apolipoprotein B level (90 vs 84 mg/dl). In logistic regression analysis only BMI and lipoprotein(a) were significant in predicting future cardiovascular events in children. Obese, hypertensive and diabetic children often come from families with cardiovascular diseases. Hypertension is the most often prevalent atherosclerosis risk factor in families. Children with positive family history of cardiovascular diseases have significantly higher body mass index. Out of new atherosclerosis risk factors lipoprotein(a) and apolipoprotein B may have real value in predicting future cardiovascular disease in the child. The aim of the study was to compare obese, hypertensive and diabetic children with positive and negative family history of cardiovascular diseases. In the work we have tried to find which of the new atherosclerosis risk factors may have the real value in predicting future cardiovascular events in children already predisposed to atherosclerosis.
 ...
PMID:[Correlation between body mass index, lipoprotein (a) level and positive family history of cardiovascular diseases in children and adolescents with obesity, hypertension and diabetes]. 1199 45

In Italy (130,000 new strokes in the general population per year) ischemic stroke is the third cause of death, after cardiovascular disease and neoplastic disease with a prevalence of 6.5%. Different physicians are involved in the emergent evaluation and treatment of the acute ischemic stroke. As other acute events, the initial evaluation must be addressed to assess the patient's airway and breath-ing and cardiocirculatory conditions. The neurological examination must not be exhaustive and it should be completed in 5-10 minutes and a particular attention should be given to clinical findings leading to the suspect of an intracranial hemorrhages. A plain CT scan of the brain is the most important initial diagnostic study. Emergency therapy must be mainly directed to the correction of hypovolemia, hypoxia and the treatment of severe hypertension, hypoglycemia, intracranial hypertension and seizures. The goal is to achieve and to maintain an adequate cerebral perfusion by lowering the intracranial pressure (treating the cerebral oedema) and by increasing the mean arterial pressure, with an appropriate volemic expansion and/or with inotropic or vasopressor drugs. The thrombolytic therapy with intravenous recombinant tessutal plasminogen activator (r-TPA) when not specifically contraindicated, is recommended within 3 hours of onset of ischemic stroke. The benefit of intravenous r-TPA for acute ischemic stroke beyond 3 hours from the onset has never been proved.
 ...
PMID:Stroke patients, what to do and what to avoid. 1202 99

The aim of this study was to determine differences in atherothrombotic risk factors in South Asian subjects with a history of ischaemic stroke and South Asian subjects free from personal and family history of clinically detectable stroke. Eighty South Asian patients with ischaemic stroke (confirmed on cranial computerised scan) and 80 South Asian controls with similar age and gender distributions were recruited at random. The frequency of hypertension (P=<0.0001), myocardial infarction (P=0.003) and diabetes mellitus (<0.0001) were significantly higher in stroke patients. Stroke patients had lower high-density lipoprotein cholesterol (0.95 vs. 1.1 mmol/l, P=<0.0001), higher plasma glucose (8.1 vs. 6.6 mmol/l, P=0.01) and trendwise higher HBA(1C) (6.4 vs. 6.0%, P=0.09). There was no difference in insulin levels but insulin resistance was significantly higher in stroke patients (3.75 vs. 2.66, P=0.01). Stroke patients showed elevated levels of fibrinogen (3.78 vs. 3.41 mg/dl, P=0.02), von Willebrand factor (1.78 vs. 1.50 IU/ml, P=0.006) and tissue plasminogen activator (12.8 vs. 11.3 ng/ml, P=0.04), but the differences did not persist after adjustment for glucose, triglycerides, HDL, WHR, and BMI. Higher levels of fibrinogen, von Willebrand factor and t-PA in South Asian stroke patients disappeared after adjustment for features of insulin resistance syndrome but persisted after adjustment for presence of diabetes, confirming that these changes are essentially dependant on features of insulin resistance syndrome. A prospective study would be required to elucidate the role of thrombotic risk factors in South Asians with ischaemic stroke.
 ...
PMID:Increased fibrinogen, von Willebrand factor and tissue plasminogen activator levels in insulin resistant South Asian patients with ischaemic stroke. 1205 85

Recent studies have indicated that a number of factors contribute to the pathophysiology in response to nitric oxide synthase (NOS) inhibition. We previously demonstrated that plasminogen activator inhibitor-1 deficient (PAI-1-/-) mice are protected against hypertension and perivascular fibrosis induced by relatively short-term NOS inhibition. In this study, we compared the temporal changes in systolic blood pressure and coronary perivascular fibrosis induced by long-term treatment with N(omega)-nitro- L -arginine methyl ester (L -NAME) in wild type (WT), PAI-1(-/-) and tissue-type plasminogen activator deficient (t-PA-/-) mice. After initiating L -NAME, systolic blood pressure increased in all groups at 2 weeks. Over a 16 week study period, systolic blood pressure increased to 143+/-3 mmHg (mean+/-SEM) in WT animals, 139+/-2 in t-PA-/- mice vs 129+/-2 in PAI-1-/- mice (P < 0.01). Coronary perivascular fibrosis increased in L -NAME-treated WT and t-PA(-/-) mice compared to each control group (P<0.01 in WT, P<0.05 in t-PA-/-), while PAI-1-/- mice were protected against fibrosis induced by L -NAME. t-PA deficiency did not accentuate the vascular pathology or the changes in blood pressure. In situ zymography demonstrated augmented gelatinolytic activity in PAI-1-/- mice at baseline, suggesting that PAI-1 deficiency prevents the increase of collagen deposition by promoting matrix degradation. Plasma TGF-beta1 levels increased in L -NAME-treated WT and PAI-1-/- mice (P < 0.01), but not in L -NAME-treated t-PA-/- mice. These findings support the hypothesis that the plasminogen activator system protects against the structural vascular changes induced by long-term NOS inhibition. While PAI-1 deficiency protects against L -NAME-induced hypertension and perivascular fibrosis, t-PA deficiency does not exacerbate the vascular pathology or hypertension.
 ...
PMID:Potential roles of plasminogen activator system in coronary vascular remodeling induced by long-term nitric oxide synthase inhibition. 1205 49

Although hypertension, hyperlipidemia, diabetes and smoking are known risk factors of atherosclerosis in Caucasians, their relative contributions to early atherosclerosis among Japanese are unknown. Decrease in flow-mediated dilation (FMD) of the brachial artery is a useful marker of endothelial dysfunction and early atherosclerosis. To evaluate the relative contribution of hypertension to early atherogenesis, we determined FMD, as well as plasma levels of tissue-type plasminogen activator (t-PA; a sensitive index of endothelial damage) and tumor necrosis factor (TNF)-a and interleukin (IL)-6 (established markers of inflammation) in normotensive and hypertensive patients under treatment. FMD was significantly reduced as the number of risk factors increased, suggesting that accumulations of risk factors were related to endothelial dysfunction. FMD was reduced in hypertensives (9.9 +/- 5.8 (SD) %) compared to normotensives (14.6 +/- 7.6, p<0.01) despite good blood pressure control (139 +/- 20/80 +/- 14 mmHg in hypertensives). Nitroglycerine-induced endothelium-independent vasodilation was not altered in hypertensives (16.0 +/- 6.3%) as compared to normotensives (16.7 +/- 5.8). Plasma t-PA, TNF-alpha, and IL-6 levels were increased in hypertensives despite good blood pressure control. Thus, hypertension alone is a high risk for early atherosclerosis. Persistent endothelial damage and moderate inflammation may increase the risk of early atherosclerosis synergistically under the presence of hypertension in Japanese.
 ...
PMID:Association of cardiovascular risk factors and endothelial dysfunction in japanese hypertensive patients: implications for early atherosclerosis. 1213 29


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>