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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 1% of the patients with cor pulmonale the cause of the high pulmonary artery pressure remains unclear. The underlying severe and mostly progressive pulmonary vascular disease with unknown aetiology is defined as primary pulmonary hypertension (PPH) with three different pathomorphological subtypes, plexogenic pulmonary arteriopathy (PPA), thrombotic pulmonary arteriopathy (TPA) and pulmonary venoocclusive disease (PVOD). The endemic occurrence of PPH after the ingestion of anorexigenic drugs (aminorex fumarate) and toxic rapeseed oil lead to the hypothesis that PPH is a pulmonary vascular reaction to exogenous toxic agents on the base of a genetic disposition. The initial response could be an endothelial cell dysfunction leading to pathological proliferation of vascular smooth muscle cells, vasospasm and local disturbances of haemostasis. The derived therapeutic concepts with vasodilators (high dose calcium channel-blocking therapy, prostacyclin) and with anticoagulant drugs show some encouraging results. The lung and heart-lung transplantation have become real therapeutic options for the patients with PPH considering the mostly still very unfavourable prognosis of PPH.
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PMID:[Primary pulmonary hypertension]. 829 Dec 74

1. The endothelium makes a significant contribution to the regulation of vascular tone through the release of potent vasodilator agents such as nitric oxide (NO) and prostacyclin (PGI2) as well as vasoconstrictor compounds such as endothelin. Recognition of this function of the endothelium has created a new focus for the investigation of vasoconstrictor activity under physiological and pathological conditions. 2. It has been well established that removal of the endothelium enhances responses to a variety of contractile agents in conductance arteries and that such modulation is predominantly due to the release of NO. The use of selective inhibitors of NO synthesis has confirmed that the endothelium-derived nitric oxide also modulates constriction in resistance vessels. 3. In a number of cardiovascular disease states there is impairment of endothelial function. Thus one of the consequences of atherosclerosis, hypertension and ischaemia is a reduction in endothelium-dependent vasodilatation, both at a basal level and in response to endogenous and exogenous stimuli. In addition, enhanced responses to vasoconstrictors have been reported in those disease states. Such observations have led to the attractive hypothesis that enhanced constriction in vascular disease results from attenuate NO-induced dilatation. However, whilst there is some evidence that pathological impairment of endothelial function is accompanied by increased constrictor activity, particularly where serotonergic mechanisms are involved, it is inappropriate to make the general assumption that where disease impairs NO activity there will also be increased sensitivity to all constrictor stimuli.
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PMID:Modulation of vasoconstriction by endothelium-derived nitric oxide: the influence of vascular disease. 854 68

Hypertension is an important cardiovascular risk factor. High blood pressure per se is not a disease but a hemodynamic alteration associated with vascular disease. Two classes of drugs are especially effective in lowering blood pressure and preventing cardiovascular complications, angiotensin converting enzyme (ACE) inhibitors and calcium antagonists. The hemodynamic effects of ACE inhibitors and calcium antagonists are complementary. While ACE inhibitors inhibit the renin-angiotensin system and reduce sympathetic outflow, calcium antagonists dilate large conduit and resistance arteries. Certain calcium antagonists, such as verapamil, lower heart rate. In the blood vessel wall, the local vascular effects of ACE inhibitors and calcium antagonists are also complementary. While ACE inhibitors inhibit activation of angiotensin I into angiotensin II and prevent the breakdown of bradykinin (which stimulates nitric oxide and prostacyclin formation), calcium antagonists inhibit the effects of vasoconstrictor hormones such as angiotensin II at the level of vascular smooth muscle by reducing calcium inflow and facilitating the vasodilator effects of nitric oxide. Calcium antagonists reduce smooth muscle cell proliferation and atherosclerosis. In hypertensive animals, verapamil and trandolapril normalize endothelial dysfunction. In large angiographic trials, nifedipine and nicardipine reduced the development of new atherosclerotic plaques. After myocardial infarction, verapamil reduces mortality and cardiac events in patients without heart failure. In contrast, ACE inhibitors are effective after myocardial infarction in patients with impaired left ventricular function. Urinary albumin excretion rate decreases during ACE inhibitor therapy or with a calcium antagonist such as verapamil; combination of the two drugs has an additive effect. In resistance arteries, hypertension is associated with an increased media/lumen ratio. ACE inhibitors, but not beta-blockers, markedly improve these structural changes. In summary, ACE inhibitors and calcium antagonists have a complementary profile, both in their hemodynamic and local vascular action. Hence, combination therapy with these two classes of drugs appears particularly useful in patients with hypertension, not only to lower blood pressure, but hopefully to achieve improved cardiovascular protection.
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PMID:Vascular protective effects of ACE inhibitors and calcium antagonists: theoretical basis for a combination therapy in hypertension and other cardiovascular diseases. 856 68

The effect of the short-term administration of beraprost sodium, an analogue of prostaglandin I2 (PGI2), on the function of vascular endothelial cells and platelet in non-insulin-dependent diabetes mellitus (NIDDM) patients was investigated. Seven nonobese NIDDM patients with microalbuminuria were recruited for this study. They received a dose of 20 micrograms of beraprost sodium three times daily for 1 month. Before and after this treatment, various factors concerning functions of vascular endothelial cells and platelet were measured. Treatment with PGI2 analogue caused a decrease in basal levels of plasma lipoprotein (a) from 16.8 +/- 5.3 to 13.2 +/- 4.4 mg/dL (p < 0.05), immunoreactive-(i)endothelin from 2.4 +/- 0.3 to 1.6 +/- 0.2 pg/mL, and i-thrombomudulin from 9.3 +/- 3.7 to 7.9 +/- 3.0 FU/L, respectively, and caused a significant increase in basal plasma i-tissue type plasminogen activator (tPA) from 5.3 +/- 0.7 to 8.3 +/- 1.5 ng/mL (p < 0.01). This treatment also increased maximum response of i-tPA induced by desmopressin infusion. Platelet aggregation due to ADP was inhibited in five of six patients after this treatment. In conclusion, treatment with PGI2 analogue caused a decrease in the presumed promoting factors of angiopathy such as lipoprotein (a) and endothelin and an increase in the protecting endothelial factor of angiopathy, tissue type plasminogen activator in patients with NIDDM. And immunoreactive thrombomodulin levels which reflect the vascular endothelial cell injury tended to decrease with the treatment. Therefore, it is suggested that this treatment preserves the vascular endothelial function in diabetes.
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PMID:The effect of PGI2 analogue on vascular endothelial function and platelet aggregation in patients with NIDDM. 857 59

Earlier studies in diabetic animal models or ex vivo from diabetics suggest a deficiency in prostacyclin (PGI2) production and an increase in an alternate arachidonic acid metabolite, 12-hydroxyeicosatetraenoic acid (12-HETE), which stimulates angiogenesis, mitogenesis, and inhibits renin secretion. We studied the urinary excretion rate of 6-keto-PGF1 alpha (a stable metabolite of PGI2) and 12-HETE in controls and 42 noninsulin-dependent diabetes mellitus (NIDDM) patients with normal renal function and those with micro- or macroalbuminuria/hyporeninemic hypoaldosteronism (HH). The 2 eicosanoids were measured in urine using previously described high pressure liquid chromatography and RIA methods. Normal subjects and patients with NIDDM and microalbuminuria were infused with low dose calcium infusions that stimulate prostacyclin production in normal subjects. The PGI2 excretion rate of NIDDM patients with normal renal function was not different from that of controls (143 +/- 17 vs. 118 +/- 34 ng/g creatinine), but was reduced in those with microalbuminuria (75 +/- 10) and in macroalbuminuria patients (48 +/- 7; P < 0.01). In contrast, 12-HETE was increased in diabetics with normal renal function as well as in those with micro- or macroalbuminuria patients (69 +/- 18 vs. 250 +/- 62 vs. 226 +/- 60 and 404 +/- 131 ng/g creatinine; P < 0.01). Calcium did not stimulate PGI2, but increased 12-HETE in diabetics with microalbuminuria in contrast to levels in normal subjects. HH patients excreted less PGI2 (as previously reported), but had increased 12-HETE. HETE/PGI2 ratios further demonstrated these changes in the various groups. In a nondiabetic hypertensive microalbuminuria group, 12-HETE excretion was normal (73 +/- 28 ng/g creatinine). We conclude that the lipoxygenase product 12-HETE is increased early in the diabetic process, whereas PGI2 production is progressively impaired in NIDDM. These changes may play a role in the vascular disease of diabetes and partially explain the HH syndrome.
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PMID:A 12-lipoxygenase product, 12-hydroxyeicosatetraenoic acid, is increased in diabetics with incipient and early renal disease. 862 61

The vascular endothelium regulates the tone of the underlying smooth muscle and the reactivity of blood elements such as platelets and neutrophils by the release of mediators, in particular nitric oxide, prostacyclin and endothelin-1. The first two of these are potent vasodilators which also inhibit platelet and neutrophil aggregation and adhesion, while endothelin-1 is the most potent mammalian vasoconstrictor peptite yet found. There are also interactions between these mediators. For instance, endothelin-1 acts on specific receptors on the endothelium to increase the release of nitric oxide and prostacyclin, while nitric oxide depresses the production and/or release of endothelin-1 from endothelial cells. Endothelin-1 and prostacyclin do not appear to be involved in the basal regulation of blood pressure whereas nitric oxide does for inhibition of its production in normotensive animals produces a marked elevation in blood pressure. Conversely, numerous vascular disease states have been associated with elevations in the production and/or release of endothelin-1 and it has been implicated in the deleterious changes associated with ischaemia/reperfusion injury, subarachnoid haemorrhage and hypertension. Endothelin-1 has also been proposed to be pro-atherogenic, as have reductions in the production of the vasodilator mediators nitric oxide and prostacyclin.
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PMID:Influence of endothelial mediators on the vascular smooth muscle and circulating platelets and blood cells. 880 31

Nitric oxide (NO), derived from the vascular endothelium or other cells of the cardiovascular system, has an important role in physiological regulation of blood flow and has pathophysiological functions in cardiovascular disease. The mechanisms and enzymes involved in the biosynthesis of NO and biological actions of NO, including vasodilatation, cytotoxicity and inflammation, are briefly reviewed. These reactions involving NO cause pathological disturbances of arterial function, coronary blood flow regulation, and may contribute to cardiac myocyte dysfunction. NO and prostacyclin (PGI2), which is also released from the endothelium, act synergistically to inhibit platelet aggregation and adhesion, and in some arteries these mediators also synergise in terms of vasodilatation. In addition, NO is capable of hyperpolarizing vascular smooth muscle, but activation of the endothelium may cause hyperpolarization and may thus promote vasodilatation by an additional mechanism. After myocardial ischemia and reperfusion, production of NO and superoxide radicals represent important mechanisms of cytotoxicity, causing injury to the coronary endothelium and myocytes and compromising ventricular contractile function. Moreover, upon reperfusion endothelium-dependent vasodilatation is impaired and the coronary arteries constrict, leading to irregular myocardial perfusion. This is a consequence of the accumulation of activated leucocytes that we found to generate endogenous inhibitors of NO. These factors have yet to be fully characterised, but clearly they may have a role in irregularities of myocardial reperfusion and cellular injury. Chronic heart failure is associated both with impairment of endothelium-dependent vasodilatation and with excess production of NO via the inducible NO synthase (iNOS), although it is unclear whether the latter assists or compromises ventricular contractile performance under these conditions. Disturbances in the activity of isoforms of NO synthase in the artery wall also accompany the development of atherosclerosis, providing conditions propitious for vasospasm and thrombosis, and perhaps contributing to cell proliferation. Reversing these NO defects with therapeutic agents including angiotensin converting enzyme (ACE) inhibitors offers promise in protecting against some manifestations of vascular disease.
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PMID:Nitric oxide in coronary artery disease: roles in atherosclerosis, myocardial reperfusion and heart failure. 880 87

Defibrotide, a polydeoxyribonucleotide, has been found to modulate endothelial cell function, causing an increase in tissue plasminogen activator (t-PA) levels, a decrease in plasminogen activator inhibitor (PAI) levels, and an increase in prostaglandin I2 (PGI2) formation in humans. Defibrotide has no direct anticoagulant effect but has a synergistic action with heparin. A strong antithrombotic effect has been observed in animal models. Thus, defibrotide has a beneficial effect in cases of deep venous thrombosis (DVT), peripheral obliterative vascular disorder (POVD), stroke, vasculitis, and thromboembolism. Defibrotide also inhibits platelet function and activation. A significant decrease in platelet aggregate formation on the suture line in microarterial anastomosis in rats is one way defibrotide can inhibit platelet function and activation. In humans, a slight prolongation' of the lag period in collagen-induced aggregation has been observed. In addition, a slight decrease in the maximum amplitude of the secondary wave of ADP and adrenalin-induced aggregations was also found. Platelet adhesion is diminished, the platelet differential count on formvar membrane is altered, and platelet aggregate formation is significantly inhibited. With an increase in platelet cyclic AMP (cAMP) content and a decrease in malonyl dialdehyde (MDA) and thromboxane B2 (TXB2) formation, the levels of platelet secretion products such as PF-4 and beta-thromboglobulin (beta-TG) in plasma decreased progressively. It was also demonstrated that the 14C-glucose transport defect of the platelet membrane of atherosclerotic patients was partially corrected with defibrotide treatment.
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PMID:Effect of defibrotide on platelet function. 880 24

The cardiovascular system is regulated by the central mechanisms, hormones and local vascular mediators. Anatomically, the endothelium lies between smooth muscle cells of the blood vessel wall and the circulating platelets and monocytes. In response to mechanical and humoral signals, endothelial cells release mediators modulating contraction and proliferation of vascular smooth muscle, platelet adhesion and aggregation, coagulation and monocyte adhesion. Nitric oxide (NO), prostacyclin and a putative hyperpolarizing factor mediate relaxation. NO also inhibits smooth muscle migration and proliferation and, together with prostacyclin, platelet adhesion and aggregation. Endothelin-1, thromboxane A2 and prostaglandin H2 are endothelium-derived contracting factors. In contrast to thromboxane A2 and prostaglandin H2 which activate platelets, endothelin-1 has no direct platelet effects, but has proliferative properties in vascular smooth muscle. Under physiological conditions, the endothelium exerts vascular protective effects as it prevents adhesion of blood cells, dilates the vasculature and inhibits vascular smooth muscle proliferation. In disease states, however, endothelial dysfunction mediates vasoconstriction, adhesion of platelets and monocytes and proliferation of vascular smooth muscle cells, all events known to contribute to atherosclerotic vascular disease.
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PMID:The pathogenesis of cardiovascular disease: role of the endothelium as a target and mediator. 882 68

Patients with the antiphospholipid syndrome as well as those with a lack in the prostacyclin synthesis stimulating plasma factor (PF) are prone to develop thrombophilia and are at a higher clinical risk for vascular disease. As patients with the antiphospholipid syndrome have been reported to show elevated lipoprotein (Lp)(a) levels, we re-examined all our patients known to have an inborn or an acquired persistent deficiency of PF. Their non-affected relatives served as controls. In addition, 36 patients suffering from clinically manifested atherosclerosis as well as 16 healthy adults, all of them having elevated Lp(a) levels (> 30 mg/dl), were screened for a PF deficiency. In fact, all the patients with a deficient PF activity showed elevated Lp(a) values. While the prevalence of PF deficiency ranges about 1-2%, in 7 (19%) patients with clinically manifested atherosclerosis and 3 (19%) healthy adults with elevated Lp(a) this defect was found. The findings demonstrate an association between PF deficiency and Lp(a), indicating a biochemical interaction which needs to be further elucidated.
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PMID:Is a (n inborn) deficiency of prostacyclin synthesis stimulating plasma factor associated with increased lipoprotein(a)? 898 34


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