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

A study was performed to investigate if oral dosing of captopril could influence the development of atherosclerosis in cholesterol-fed cynomolgus monkeys. Twenty-four monkeys were divided into four groups: (a) a control group given a normal monkey diet and placebo medication; (b) a high cholesterol group given a high cholesterol diet and placebo medication; (c) a low-dose captopril group given the cholesterol diet and 25 mg/kg of captopril twice daily; and (d) a high-dose captopril group given the cholesterol diet and 50 mg/kg of captopril twice daily. The doses of captopril used in this study did not change the levels of total serum cholesterol, high-density lipoprotein (HDL), or triglycerides. The total cholesterol/HDL ratio was also unaffected by captopril. The animals were killed after 6 months of treatment. The progression of atherosclerosis was assessed by gross pathology, histopathology, and biochemical methods. The results showed a significantly reduced progression of arterial lesions in monkeys given captopril; the effects of captopril were most evident in the coronary arteries, which were practically free from atherosclerosis in captopril-treated animals.
J Cardiovasc Pharmacol 1990
PMID:Effects of captopril on atherosclerosis in cynomolgus monkeys. 169 34

Obvious, but often forgotten, is the premise that blood pressure reduction in the patient with hypertension is a surrogate for our real goal, which is reduction in the risks consequent to hypertension. This surrogate, a convenience for regulatory agencies, has therapeutic implications. As the array of antihypertensive agents available has grown, along with information from clinical trials and insights into underlying mechanisms, it has become reasonable to examine that premise. The overall success of antihypertensive therapy has been undeniable, but has not influenced the advance of atherosclerosis, primarily coronary events. Multiple observations suggest that metabolic disarray consequent to the use of antihypertensive agents, especially thiazides and beta-blockers, may have contributed to this scenario. Electrolyte abnormalities predispose to malignant arrhythmias and sudden death during myocardial infarction. Left ventricular hypertrophy, a major risk factor for coronary events, arrhythmias, and heart failure, responds selectively to antihypertensive agents. Similarly, the progression of renal injury in the hypertensive patient may be sensitive to the agents employed. Obesity and hypertension coexist frequently; moreover, evidence is growing that atherogenic abnormalities common in the obese patient, such as insulin resistance, not only occur frequently in the nonobese patient, but are also sensitive to the antihypertensive agent selected. Although predictions are risky, it seems safe to predict that the next chapter in antihypertensive therapy will examine whether we need to go beyond blood pressure reduction in selecting such therapy.
J Cardiovasc Pharmacol 1990
PMID:Management of hypertension: considerations involving cardiovascular risk reduction. 169 35

Hypertension is a major risk factor for atherosclerosis. Although antihypertensive drug treatment can reduce morbidity and mortality from stroke, there is no consistent benefit on ischemic heart disease. It may be that subtle adverse effects of the drugs used in these clinical trials may have blunted the beneficial effects of treatment. Isradipine, a new calcium antagonist of the dihydropyridine class, is a potent antihypertensive drug with pronounced antiatherogenic properties, at least in animal studies. Thus, isradipine may be a suitable drug for assessing the efficacy of antihypertensive treatment in retarding the progression of atherosclerosis. The Multicenter Isradipine/Diuretic Atherosclerosis Study (MIDAS) is a clinical trial to compare the efficacy of isradipine (2.5-5.0 mg b.i.d.) and hydrochlorothiazide (12.5-25 mg b.i.d.) in retarding atherosclerosis in carotid arteries. Carotid atherosclerosis will be monitored using B-mode ultrasonography. The sample size is 800 men and women aged 40 years and over. The power of the design is 90% to detect a 30% difference in the progression of plaque size between the isradipine- and hydrochlorothiazide-treated groups with a significance level of 5% (p = 0.05).
J Cardiovasc Pharmacol 1990
PMID:Multicenter study with isradipine and diuretics against atherosclerosis. US MIDAS Research Group. 169 98

Ultrasound has become a well-established method for the clinical evaluation of carotid artery atherosclerosis. In the past few years, high-resolution ultrasound methods have been used more frequently in the study of the natural history of atherosclerosis. Most recently, B-mode ultrasound has enabled investigators to detect and monitor early stages of carotid artery atherosclerosis, when lumen stenosis is between 15 and 45%. Epidemiological studies using high-resolution ultrasonography will allow researchers to correlate traditional risk factors for atherosclerosis with changes over time in lesion incidence, prevalence, and severity. Investigators can also study the effects of drug treatment on the early stages of disease by monitoring rates of lesion progression or regression in carotid arteries. Several large epidemiological and clinical intervention trials are currently underway that use high-resolution B-mode ultrasonography to measure intima-media or total wall thicknesses in extracranial carotid arteries. In these studies, the reproducibility of arterial wall measurements is the most critical factor in establishing rates of lesion progression or regression. This paper describes the ultrasound methods currently being used to determine the effect of the calcium antagonist, isradipine, on patients with asymptomatic carotid artery atherosclerosis.
J Cardiovasc Pharmacol 1990
PMID:Interventional clinical trials using noninvasive ultrasound end points: the Multicenter Isradipine/Diuretic Atherosclerosis Study. The MIDAS Research Group. 169 99

Calcium antagonists retard the development of atherosclerosis in cholesterol-fed rabbits and modestly enhance regression after their return to a normal diet. Proliferative lesions following endothelial damage (from, for example, balloon catheter, electrical stimulation) are also diminished. Many mechanisms for these effects have been proposed and their relative importance is not yet clear. However, changes in blood lipid levels do not play an important role. Only a few investigations into how atherosclerosis affects the hemodynamic actions of calcium antagonists have been carried out. Thus, the effects of isradipine were compared in atherosclerotic and normal rabbits. Isradipine increased heart rate and cardiac output less in atherosclerotic rabbits than in normal ones while having no effect on the surface electrocardiogram (ECG). In contrast, the arteriolar vasodilator, dihydralazine, induced ST-segment depression with similar falls in blood pressure, partly explainable by reflex tachycardia and intramyocardial maldistribution of coronary blood flow. Flow to the brain increased with isradipine and decreased with dihydralazine. In atherosclerotic animals, the pressor effects of norepinephrine, phenylephrine, and angiotensin II (Ang II) were amplified. Isradipine partly corrected this enhanced responsiveness. Calcium antagonists thus elicit beneficial hemodynamic and antivasoconstrictor effects in atherosclerotic experimental animals, in addition to having a long-term prophylactic antiatherosclerotic action.
J Cardiovasc Pharmacol 1990
PMID:Hemodynamic, antivasoconstrictor, and antiatherosclerotic effects of calcium antagonists in animal models of atherosclerosis. 169 7

A role for angiotensin II (Ang II) in the pathogenesis of hypertension and atherosclerosis was studied using cultured vascular smooth muscle cells from spontaneously hypertensive rats. Chronic exposure of vascular smooth muscle cells, cultured in the presence of 1% plasma-derived serum, to Ang II resulted in a dose-dependent stimulation in growth and incorporation of radiolabeled matrix precursors into extracellular matrix-associated glycoconjugate material. The hormone also stimulated the incorporation of [3H]glycine into extracellular matrix glycoproteins and proteoglycans synthesized by cultures rendered quiescent by maintenance on serum-free medium for 48 h prior to exposure to Ang II. This was negated in the presence of saralasin. In quiescent cultures, a single exposure to angiotensin induced a rapid induction of mRNA coding for the extracellular matrix glycoprotein thrombospondin. Similar results were obtained with cells maintained on medium containing 1% plasma-derived serum; however, the levels of induction were reduced by this procedure. This study demonstrated that Ang II was capable of stimulating both growth and matrix elaboration by cultured vascular smooth muscle cells. These observations are indicative of a pathophysiological role for the vasoconstrictor peptide, which may contribute significantly to the development of hypertension.
J Cardiovasc Pharmacol 1990
PMID:Modulation of extracellular matrix by angiotensin II: stimulated glycoconjugate synthesis and growth in vascular smooth muscle cells. 170 26

There is evidence that calcium antagonists (calcium channel blockers) may suppress atheroma formation in animals fed high-fat diets. Studies on the antiatherosclerotic effects of calcium blockers have suggested a variety of possible mechanisms: (a) lowering of arterial pressure, (b) decrease in atherogenic plasma lipoproteins, (c) suppression of accumulation of intracellular lipids, (d) suppression of atherogenic platelet dysfunction, (e) prevention of dyslipidemic endothelial injury, (f) inhibition of chemotaxis and cell migration, (g) inhibition of cell proliferation, (h) inhibition of deposition of matrix proteins, (i) suppression of tissue mineralization, and (j) retardation of cell necrosis. Although it is tempting to ascribe the antiatherosclerotic effects of calcium blockers to a blockade of calcium channels, other possible common mechanisms of action involving low-affinity drug-binding sites must be considered. Recently, two randomized, prospective clinical trials designed to determine the effects of calcium channel blockers on the progression of coronary artery disease have been completed. Results of the trials suggest that calcium channel blockers suppressed the progression of coronary atherosclerosis. The utility of calcium channel blockers for the treatment of atherosclerosis will require further evaluation.
J Cardiovasc Pharmacol 1990
PMID:Calcium channel blockers and atherosclerosis. 170 8

We have studied the relationship between the early morphological changes and arterial responsiveness to vasoactive agents in a new animal model that is proposed to mimic the events of early human atherosclerosis. Atheroma-like lesions were produced by positioning a hollow Silastic collar (referred to as a cuff) around the common carotid arteries of rabbits. Following a period of either 48 h or 1, 2, or 4 weeks after surgery, vessels from both cuffed and sham-operated animals were removed, and vascular reactivity to cumulative concentrations of agonists were studied in isolated rings in organ baths. The contralateral arteries were perfused and fixed, studied by light microscopy, and the degree of intimal thickening was quantified by computer-assisted morphometric analysis and expressed as changes in the ratios of the cross-sectional areas of the intima and media in each artery. At 48 h, rings prepared from cuffed arteries were sixfold more sensitive to the contractile effects of serotonin (5-HT) than the corresponding controls. Histologically, such vessels showed some perivascular inflammation but no other morphological abnormality. At 7 days, cuffed vessels were again sixfold more sensitive to 5-HT than controls, and showed a thickened intima with marked smooth muscle proliferation and some infiltration by monocytes. Intimal/medial cross-sectional area ratios remained elevated at 2 and 4 weeks, but the supersensitivity to 5-HT diminished by 2 weeks to threefold and was absent at 4 weeks. The augmented reactivity to 5-HT at 48 h was specific, in that it did not occur for the alpha-adrenoceptor agonist, phenylephrine.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1990 Oct
PMID:Supersensitivity to vasoconstrictor action of serotonin precedes the development of atheroma-like lesions in the rabbit. 170 11

Many detailed studies have demonstrated that calcium antagonists can suppress development of diet-induced atherosclerosis in the thoracic aorta of animals. A number of possible mechanisms have been proposed based on in vitro work, but the exact mechanism remains unclear. Alteration of serum lipid levels and blood pressure does not appear to be the common pathway. Differing effects between calcium antagonists of different classes indicate that the voltage-dependent calcium channel-blocking action common to all calcium antagonists is not the sole mechanism. Preliminary results of several major quantitative angiographic studies in human coronary artery disease have recently become available and indicate that calcium antagonists are able to retard the progression of existing lesions in humans also. There is also evidence that calcium antagonists may prevent the development of new lesions and, in some cases, induce lesion regression. Longer follow-up and further trials are required to assess the appropriateness of widespread clinical application of these agents in coronary artery disease, to determine the optimal timing for their introduction, and to define their mechanism of action in influencing the natural history of atherosclerosis.
J Cardiovasc Pharmacol 1990
PMID:A review of calcium antagonists and atherosclerosis. 170 12

It is now recognized that dietary and other lifestyle or environmental factors are critical for the phenotypic expression of a genetic predisposition to blood pressure (BP) elevation. These environmental factors influence the entire frequency distribution of BPs in any given population, and hence affect the prevalence of hypertension using whatever arbitrary cutoff point is chosen to categorize patients in this way. "Dose-response" relationships with BP have been demonstrated with body fat, alcohol consumption, sodium intake, vegetarian vs. meat-related diets, and physical activity. Possible relationships between these and other "environmental" factors have not yet been fully clarified, although this is of considerable importance for primary prevention of hypertension as well as for specifying advice for individual patients. Knowledge of the extent to which varying dietary or other lifestyle factors operate in different patients is also likely to be necessary for those trying to resolve the nature of the pathophysiological and genetic mechanisms underlying high BP. Finally, several of the factors causing hypertension independently predispose to atherosclerosis, and have compounded the risk of cardiovascular disease in hypertensive patients.
J Cardiovasc Pharmacol 1990
PMID:Diet and lifestyle in hypertension: changing perspectives. 170 29


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