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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension and hypercholesterolemia predispose to atherosclerosis. Ramipril, known to lower blood pressure, was used to study the effect of converting-enzyme inhibition on impairment of endothelium-derived relaxation and changes in basal cGMP content in rabbits fed an atherogenic diet (0.25% cholesterol). The generation of cGMP in the presence of bradykinin and ramiprilat was studied in vitro in aortic segments from normal untreated rabbits as well as in bovine endothelial cells. The ability to relax in response to acetylcholine was almost abolished in aortic segments from the vehicle-treated rabbits fed the atherogenic diet for 4 months. The basal cGMP content was substantially reduced. Aortic segments from rabbits concomitantly treated with ramipril (0.3 and 3.0 mg/kg/day) for 3 months showed well-preserved relaxation and matching basal cGMP content compared to normal controls. The relaxation was not significantly greater in aortic segments from ramipril-treated rabbits fed the standard diet, but the cGMP content was more than doubled. In vitro studies in aortic segments and in endothelial cells showed that both the ramiprilat and bradykinin concentrations dependently stimulated cGMP formation, which serves as a biochemical marker of nitric oxide or EDRF release. Thus, the observed endothelial protection against hypercholesterolemia by ramipril may be the result of continuously increased cGMP formation due to preserved EDRF release. This is presumably produced by enhanced bradykinin activity through inhibition of degradation by converting-enzyme inhibition with ramipril.
J Cardiovasc Pharmacol 1991
PMID:Preservation of endothelial function by ramipril in rabbits on a long-term atherogenic diet. 172 17

To date, a range of drugs are available that are generally well tolerated and effective in lowering blood pressure. Although they are successful in reducing stroke, renal failure, and cardiac failure, they have a disappointing and less than expected influence on coronary artery disease and its manifestations. The genetic and environmental factors determining susceptibility to atherosclerosis and coronary artery disease are now more clearly defined and interactions between risk factors and protective mechanisms recognized. Drug treatment of hypertension must become a part of the overall approach to prevention of cardiovascular disease and possible health promotion. Dietary and hygienic measures (cessation of smoking and control of alcohol intake) should be combined where necessary with specific treatment of hypertension and hyperlipidemia. Future drug treatment must not only be effective and well tolerated but should complement other preventive approaches. In view of the increasing recognition that blood pressure treatment with a single drug is unlikely to be successful in all patients, there is likely to be a role in the future for pharmacologically coherent low-dose combinations of antihypertensive drugs.
J Cardiovasc Pharmacol 1991
PMID:The treatment of hypertension: a therapeutic philosophy for the 1990s. 172 46

Vascular remodeling is central to the pathophysiology of hypertension and atherosclerosis. The effects of antihypertensive drugs on this process are important to consider from a mechanistic and a pathogenetic point of view in relation to vascular complications of hypertension, e.g., decrease in vascular reserves, shift in cerebral blood flow autoregulation and atherosclerosis development. There is now evidence that, in addition to several other growth factors, vasoactive peptides such as angiotensin II may act as vascular smooth muscle growth promoting substances. Based on these data, the effects of perindopril, a potent and long-lasting angiotensin-converting enzyme (ACE) inhibitor, on structural and mechanical properties of the arterial wall, have been studied in animal models of hypertension as well as in humans. Perindopril completely reversed aortic medial hypertrophy and arterial stiffening observed in renovascular hypertensive rats. Similar benefits were reported in mesenteric resistance vessels of spontaneously hypertensive rats. The effect of perindopril was totally in keeping with potent inhibition of vascular ACE and emphasized the potential role of angiotensin II as a vascular growth modulator. Clinical studies confirmed animal experiments; both suggest that increases in arterial compliance and distensibility following perindopril is likely to be related to drug-induced modification of the arterial wall, at least partially independently of blood pressure reduction. The increase in arterial compliance was associated with a selective decrease in pulse pressure, a finding that is important, not only for the arterial wall, but also for the structure and function of the hypertensive heart.
J Cardiovasc Pharmacol 1991
PMID:Vascular effects of perindopril: from experimental to clinical investigation. 172 97

The effects of prostacyclin and its stable analogues on endothelin-induced DNA synthesis were investigated in cultured vascular smooth muscle cells. Aortic smooth muscle cells were obtained from male Wistar rats. In order to eliminate endothelial cells, the cells were cloned. DNA synthesis in intact cells was estimated by [3H]thymidine incorporation. Prostacyclin and its stable analogues (TEI-7165, TEI-9090, TEI-1324, TEI-3356, and TEI-9063) inhibited the endothelin-induced DNA synthesis with an IC50 of 1-30 nM. These results indicate that prostacyclin and its stable analogues are possibly effective in preventing the proliferation of vascular smooth muscle cells under some pathological situations, including atherosclerosis.
J Cardiovasc Pharmacol 1991
PMID:Inhibition of endothelin-1-induced DNA synthesis by prostacyclin and its stable analogues in vascular smooth muscle cells. 172 24

The distribution of endothelin-1 (ET-1) receptors on human vascular tissue has been studied. High- and low-resolution autoradiography was used to determine the distribution of [125]ET binding sites in human blood vessels and ventricular myocardium. Dense, displaceable [125I]ET binding was associated with cardiac myocytes and the smooth muscle layer of all vessels were examined. There was also dense binding to vasa vasora. There was increased [125I]ET binding to atheromatous coronary arteries and vein graft, which was associated with the tunica media and vasa vasora or regions of neovascularization. Vasoconstrictor and positive inotropic activity of ET-1 has been established in vitro. The vasoconstrictor effect of ET-1 is likely to be mediated via the binding sites identified on vascular smooth muscle. The striking perivascular [125I]ET-1 binding suggests that ET-1 may also have constrictor activity on vasa vasora. There is experimental evidence that ET-1 has mitogenic activity on vascular smooth muscle cells in culture. The increased binding to both smooth muscle and regions of neovascularization in atheromatous vessels suggests that ET-1 may play a role in atherosclerosis.
J Cardiovasc Pharmacol 1991
PMID:Autoradiographic localization of [125I]endothelin binding sites in human blood vessels and coronary tissue: functional correlates. 172 12

Atherosclerosis results from multiple factors, and involves several mechanisms including endothelial monocyte and smooth muscle cell changes, cholesterol accumulation, lumen stenosis, necrosis, mineralization, plaque hemorrhage, rupture, and thromboembolism. Calcium antagonists have been shown in hypercholesterolemic animal models to reduce atherosclerosis. This effect cannot be explained on the basis of changes in blood pressure, therefore suggesting that calcium channel antagonists have a direct effect on arterial wall processes associated with plaque evolution. The antiatherosclerosis properties of calcium antagonists have been tested in human subjects and suggest that these compounds inhibit new lesion development. Recent developments in B-mode ultrasonography allow investigators to detect and monitor atherosclerosis noninvasively. This method is being used in several trials within the U.S. and Europe to evaluate treatment effects on carotid atherosclerosis. Carotid artery disease is associated with transient ischemic attacks, ischemic cerebral infarction, and with risk for coronary artery disease. B-mode ultrasonography is a powerful method for monitoring atherosclerosis progression. The combination of this technology with calcium antagonist treatment will allow evaluation of the efficacy of intervention on the arterial wall during the asymptomatic stages of atherosclerosis evolution.
J Cardiovasc Pharmacol 1991
PMID:Antiatherogenic properties of calcium antagonists. 172 13

We have previously shown the safety and efficacy of University of Wisconsin solution for hypothermic preservation of the human donor heart in a pilot group of 16 transplant recipients. The present study is a randomized clinical trial comparing University of Wisconsin solution to conventional preservation using crystalloid cardioplegia and saline storage within a 4-hour limit of ischemia. Heart transplant recipients (n = 42) were randomized into two groups: those receiving hearts preserved by University of Wisconsin solution, the UWS group (n = 22), and those receiving hearts preserved in the conventional manner, the CCS group (n = 20). Recipient age, gender, heart disease, and preoperative inotropic support and donor age, gender, and mean ischemic time in hours (UWS 2 hours 36 minutes, range 1 hour 36 minutes to 2 hours 53 minutes; CCS 2 hours 20 minutes, range 1 hour 20 minutes to 2 hours 44 minutes; p = not significant) were similar. Significant differences observed between the two groups included (1) mean time (minutes) from reperfusion to achieve a stable rhythm, (2) need for intraoperative defibrillations, (3) need for transient cardiac pacing, and (4) integrated postoperative creatinine kinase and aspartate aminotransferase release over 48 hours. There was no difference in postoperative electrocardiogram, endomyocardial biopsy, or hemodynamics. One UWS patient died of sepsis and another of a ruptured cerebral aneurysm. UWS is safe for donor organ arrest and preservation despite high viscosity and potassium concentration. When compared with CCS hearts, hearts preserved in UWS regained electrical activity more rapidly and had better myocardial protection as demonstrated by enzymatic analysis. Further investigation is required to determine the effects of UWS preservation on long-term survival, to determine the prevalence of rejection and graft atherosclerosis, and to test the ability of UWS to extend donor ischemic time in human cardiac transplantation.
J Thorac Cardiovasc Surg 1992 Feb
PMID:University of Wisconsin solution versus crystalloid cardioplegia for human donor heart preservation. A randomized blinded prospective clinical trial. 173 83

Abdominal aortic coarctation is a rare, non-atherosclerotic disease. It is a functionally significant at an early age when associated with aortic branch stenosis and renovascular hypertension. The pathogenesis of aortic constrictive lesions remains unknown, but may be related to developmental error or aortic growth arrest and various hypotheses have been reported. When the renal arteries are involved by the coarctation, severe hypertension is common at an early age and in untreated patients, life-threatening complications commonly occur. Patients who reach the age of 40 years generally have the coarctation below the renal arteries but even when the renal arteries are not involved by the coarctation, renovascular disease may still occur due to secondary atherosclerosis. Aortic thrombosis secondary to abdominal aortic coarctation with renovascular disease and lower limb ischemia, occurring in a 63-year old woman, is reported.
J Cardiovasc Surg (Torino)
PMID:Abdominal aortic coarctation inducing aortic occlusion and renovascular hypertension. 175 97

This paper presents the long term results following operative reconstruction for renovascular hypertension in 115 patients operated upon over a period of 20 years. There were 71 (61.7%) males and 44 (38.3%) females with a median age of 46 years (range 16-67). Renal revascularization was unilateral in 96 (83.4%) cases and bilateral in 19 (16.6%). Dacron knitted bypass grafts, were used in 51 and PTFE in 33 instances. Saphenous vein grafts were used in 11 patients. In 15 cases treatment was by local endarterectomy with concomitant angioplasty (12 unilateral and 3 bilateral). Simultaneous aortorenal reconstruction was undertaken in 38 (33%) patients. There were no deaths in the group with isolated renal artery reconstruction. In the group of aortorenal reconstructions, two deaths were encountered (5.7%). Postoperatively, blood pressure was either normal or improved in 83 (72%) patients at a mean follow-up period of 48.3 months (range 1-195 months). The best results were obtained in younger individuals with segmental renal artery lesions. Linear progression analysis, showed age to be a major determinant in the postoperative response to hypertension. There was a greater degree of long term success in patients with fibromuscular dysplasia, as compared to individuals with atherosclerosis. Crude survival probabilities, were 78% and 61% at 5 and 10 years respectively. Late deaths encountered in the present series, were mostly attributable to myocardial infarction (7.8%). In this series, the best results were obtained in individuals younger than 50 years of age, with segmental renal artery lesions.
J Cardiovasc Surg (Torino)
PMID:Surgical treatment of renovascular hypertension and respective late results. A twenty years experience. 182 96

Between 1983 and 1989, 40 patients with uncontrollable hypertension underwent renal revascularization. Of these, 21 patients had simultaneous aortic and renal revascularization. Eleven of the 21 patients (52.4%) had renal insufficiency with a mean creatinine clearance of 0.61 +/- 0.23 ml/sec. Eleven patients had an aortic aneurysm; the remaining 10 patients had aortic occlusive disease of varying severity. Aortic reconstruction was done with either a straight (8 patients) or bifurcated (13 patients) Dacron graft. Renal revascularization was accomplished with either bypass (11 patients) or transaortic endarterectomy (10 patients). One patient died postoperatively secondary to myocardial infarction (operative mortality rate of 4.7%). Among the 11 patients with renal insufficiency the mean creatinine clearance of 0.61 +/- 0.23 ml/sec preoperatively improved to 0.94 +/- 0.30 ml/sec postoperatively (p less than 0.01). In the follow-up period extending to 78 months (mean 39.1 months), one late death occurred. There were no instances of worsening hypertension or deterioration in renal function. Contrary to some previous reports, our results indicate that severe aorto-renal atherosclerosis can be managed with simultaneous aortic reconstruction and renal revascularization at an acceptably low operative risk. In addition, a significant and persisting benefit in both hypertension control and renal dysfunction can be expected after surgery.
J Cardiovasc Surg (Torino)
PMID:Are simultaneous aortic reconstruction and renal revascularization safe and effective? 183 78


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