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

Hypertension results from abnormalities of the control systems that normally regulate blood pressure. These control systems include vascular, cardiogenic, renal, neurogenic, and endocrine mechanisms that interact in a complex but integrated manner to achieve blood pressure homeostasis. Multiple endogenous biologically active substances participate in the regulation of these control systems. Evidence suggests that abnormalities of these regulatory mechanisms resulting from altered genetic and environmental interactions play an important role in the pathogenesis of primary hypertension. Once hypertension develops, it tends to be self-perpetuating via amplifying mechanisms mediated by secondary structural changes in the blood vessels, heart, and kidney. These adaptative structural changes amplify and perpetuate hypertension by increasing systemic vascular resistance, enhancing cardiac output, and impairing renal sodium and water excretion. The long-term sequelae of hypertensive structural changes in these end organs are complications of atherosclerotic vascular disease, cardiac hypertrophy and failure, stroke, and renal failure. With the tools of molecular biology, our understanding of the molecular mechanisms underlying these abnormalities has increased enormously and continues to grow at a rapid pace, as illustrated by the discussion that follows. Our review of the molecular biology of hypertension will address systematically four key areas: 1) molecular biology of the control systems, 2) molecular mechanisms of cardiovascular structural changes, 3) genetics of hypertension, and 4) application of transgenic technology in studies of hypertension.
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PMID:Molecular biology of hypertension. 183 15

Based on the documented regulatory role of polyamines in cell growth and differentiation, we have proposed that these organic cations are involved with the development of monocrotaline (MCT)-induced hypertensive pulmonary vascular disease. Two lines of evidence support this hypothesis: (1) MCT causes progressive increases in lung polyamine contents which are temporarily related to the development of cardiopulmonary abnormalities, and (2) blockade of polyamine synthesis with the site-selective enzyme-activated inhibitor, alpha-difluoromethylornithine (DFMO), attenuates development of medial arterial thickening, increased pulmonary arterial pressure, and right ventricular hypertrophy. To evaluate the mechanism of DFMO protection, the present study assessed when, during the course of MCT-induced pneumotoxicity, DFMO exerts its salutary effects, and determined if the protection afforded by DFMO could be reversed through supplementation with exogenous polyamines. To address the first issue, rats were treated with 30 mg/kg MCT and, 10 days after administration when lung polyamine contents were augmented and when pulmonary edema was evident, DFMO treatment was initiated as a 2% solution in the drinking water. In animals receiving MCT only, lung polyamine contents were elevated and right ventricular hypertrophy was evident at both 20 and 35 days after treatment. DFMO treatment initiated at day 10 attenuated the increases in putrescine and spermidine but not spermine and reduced the degree of right ventricular hypertrophy at both the 20- and 35-day time points. To determine if the blockade by DFMO could be reversed by supplementation with exogenous polyamines, animals were treated simultaneously with MCT and DFMO as described above and the immediate precursor to the polyamines, ornithine, was added to the drinking water as a 2% solution. Relative to animals receiving MCT and DFMO, ornithine supplementation increased lung polyamine contents to levels normally associated with MCT treatment only. Ornithine also reversed the protection against right ventricular hypertrophy normally afforded by DFMO. These observations indicate that the salutary effects of DFMO in MCT-induced pulmonary hypertension cannot be ascribed solely to interference in the early events after MCT treatment and that restoration of lung polyamine contents to high levels by supplementation with exogenous ornithine reverses DFMO protection against sustained pulmonary hypertension. It is concluded, therefore, that polyamines play a central role in delayed responses of lung cells underlying the development of MCT-induced sustained pulmonary hypertension.
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PMID:Polyamine synthesis blockade in monocrotaline-induced pneumotoxicity. 250 77

In 1949, amphetamine sulfate was replaced by propylhexedrine in the nasal decongestant agent Benzedrex because of psychosis, sudden death, and widespread abuse. Propylhexedrine is not without risks, and reported cases of psychosis, myocardial infarction, pulmonary vascular disease and pulmonary hypertension, and sudden death are well documented in the medical literature. We are reporting 2 cases of definite brainstem dysfunction and 5 cases of transient diplopia secondary to IV abuse of Benzedrex. This widely abused drug is prepared by heating Benzedrex and hydrochloric acid, and the resulting crystals are dissolved in water for injection. This agent is called "stove-top speed". All 7 patients had transient diplopia, within seconds after injection. One patient had evidence of a right-internuclear ophthalmoplegia, and another had a depressed right gag reflex and paralysis of the right half of the tongue. The deficits in these two patients, persisted for many months. In young adults with history of drug abuse, the IV use of Benzedrex should be considered in the differential diagnosis of transient or permanent focal brainstem deficits.
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PMID:Intravenous abuse of propylhexedrine (Benzedrex) and the risk of brainstem dysfunction in young adults. 287 25

The 2-nitroimidazole, misonidazole, is of current interest as an imaging agent for hypoxic regions in tumors and in vascular disease such as stroke. The basis of this technique is the reductive activation and binding of nitroheterocycles which is much more efficient in the absence of oxygen. The appropriate molecular location for an active isotope on the nitroheterocyclic probe depends on the nature of the metabolites retained in tissues after the parent drug has been cleared. Previous studies with tumor cells in vitro indicated that a ring label (2-14C) and a side-chain label (3H) were retained equally efficiently in the acid-insoluble fraction, whereas 1.5 to 3 times more side-chain label was retained in the total pool (acid soluble plus acid insoluble) of metabolites in several normal murine tissues. We show here that the excess side-chain label in six normal tissues, plasma and EMT6 tumors was found entirely in the acid-soluble fraction as a volatile component. This volatile component was tentatively identified as tritiated water. It appeared that, in general, molecular products of misonidazole metabolism were retained in mouse tissues, with the exceptions that a small excess of ring label was found in liver and heart and that tritiated water appeared in the acid-soluble fraction of all tissues. Tritiated water would not be important in imaging studies but could be a factor in studies in which scintillation counting of tritiated nitroheterocyles is used.
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PMID:Metabolic binding of misonidazole to mouse tissues. Comparison between labels on the ring and side chain, and the production of tritiated water. 291 21

The impending release of erythropoietin (EPO) is expected to result in a dramatic increase in hematocrit (Hct) for most hemodialysis (HD) patients. Our studies indicate that as Hct rises, dialyzer mass transport for some clinically critical solutes will be adversely affected. When whole blood clearances are corrected for solute-specific blood-water flows (QBH2O), the effect on the surrogate molecule, urea, used in urea kinetic modeling (UKM) is deceptively minimal, because only urea can diffuse almost instantly from red cells into blood water. For the critical solutes, potassium and phosphate, QBH2O is reduced to Q (plasma water). With a KoA of 690 ml/min at QB = 300, clearance of potassium falls at least 19.3% as Hct rises from 20 to 40% so that steady-state predialysis potassium could rise from 6.0 to 6.95 mEq/L. Already inadequate phosphate clearance falls at least 10% and additional loss results from physical interference by RBCs with solute diffusion. Hcts are further increased with rapid weight losses during high-efficiency dialyses (0.15 per 5% weight loss in 3 hours, r = 0.82) resulting in blood-side pressures such that most dialysis machines cannot provide adequate dialysate pressures to maintain low ultrafiltration rates (UFRs) at the high QB levels. The combination of pre-existing diffuse vascular disease, postdialysis hypovolemia, hypotension, decreased cardiac output, and increased blood viscosity has and will produce disastrous syndromes of organ ischemia, thrombosis, and infarction. Predialysis hypertension can worsen. Extreme caution and adjustment of dialysis regimen is necessary as patient Hct rises above 36%.
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PMID:Erythropoietin alert: risks of high hematocrit hemodialysis. 319 6

A physical model was used to test the effects of vibrations on the position of transition to turbulence (zt) downstream of a constriction. Constrictions were inserted in a length of clear plastic (Tygon) tubing and vibrated. Water was the fluid medium and flow was visualized with India ink. The frequency and velocity of vibration were monitored. For a given constriction and flow velocity, there was a band of frequencies which caused zt to move upstream. This band corresponded to frequencies of flow disturbances as measured with a hot-film anemometer without vibration. Both flow-visualization and hot-film frequencies were correlated via a Strouhal number to the Reynolds number and contraction ratio of the flow. Values of zt decreased with increasing vibration amplitude. The critical Reynolds number for turbulence was also decreased by vibration. These results are of importance in the diagnosis of vascular disease and the design of physical models of stenotic flows.
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PMID:Effects of vibration on steady flow downstream of a stenosis. 325 76

Hypertension that is truly resistant to modern antihypertensive therapy is uncommon. In the majority of cases, apparent resistance is more likely associated with poor patient adherence, interacting drugs, drug interactions, and inappropriate drug dosages. Sodium and fluid volume play a major role in resistant hypertension. There is considerable evidence to support the role of dietary sodium restriction in successful nonpharmacological treatment of hypertension. Salt sensitivity in humans appears to represent at least one factor determining individual susceptibility to variable salt intakes. Sodium and water retention may lead to refractoriness to many antihypertensive agents, and there is evidence to suggest that extracellular fluid volume expansion also plays a role in many hypertensive patients. While retention of sodium and water is well established early in patients with renal parenchymal disease, hypertension associated with progression of renal parenchymal disease is complicated by other factors that include interactions between hemodynamic and humoral factors, functional changes in adrenergic responses, and structural vascular disease. The role of other cations such as potassium, calcium, and magnesium in resistant hypertension has yet to be established.
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PMID:The patient with resistant hypertension. Cations, volume, and renal factors. 328 Apr 98

The fetal and maternal morbidity and mortality from the hypertensive disease states of pregnancy is a major problem. While much is known about the syndrome, the cause has been elusive. The ewe was chosen to test a hypothesis that depletion of magnesium may be involved. Twelve Finnish ewes were subjected to low magnesium diets with half given magnesium in the water. Tests included measurement of blood pressure in the waking state and by noninvasive technique. Magnesium levels were measured by atomic absorption spectrophotometry in the plasma and tissue of the ear tips. Findings included significant elevation of arterial blood pressure, reduction in fetal weight with pathologic confirmation of placental and renal lesions which were similar to those seen in the human condition. Significant lowering of both plasma and tissue of magnesium was noted. The hypothesis was supported and extended to include possible interaction with prostacyclin and thromboxane as intermediaries in a hypomagnesic coagulative angiopathy. This entity would also explain the association of migraine in the eclamptic and preeclamptic syndrome reported by previous authors. The success of parenteral magnesium in the treatment of these human conditions is therefore more than purely empiric.
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PMID:Pregnancy-induced hypertension and low birth weight in magnesium-deficient ewes. 352 57

The purpose of this study was to test the hypothesis that habitual smoking of tobacco cigarettes reduces reactive hyperemia in peripheral areas of smokers who are at low risk of having atherosclerotic vascular disease. This was achieved by a cross-sectional comparison of post-occlusion hyperemia in the hand circulation of female cigarette smokers and nonsmokers in the 20- to 40-yr age range. Epidemiologic evidence indicates that sclerotic lesions are unlikely in the upper extremities of females in this age range. The right hand of a subject was maintained in a water bath at 32 degrees C while mean blood flow velocity (V) in the radial artery was measured before and after occlusion periods of 1 and 5 min. The 5-min period elicited maximal reactive hyperemia. Following both periods of occlusion the percent increase in V was less for smokers (P less than .02). Also, the absolute increase in V following 5 min of occlusion for the smokers was less than that of the nonsmokers (P less than or equal to .05). These results indicate that habitual cigarette smoking reduces peripheral vasodilatory reserve in young smokers. The fact that sclerotic lesions are unlikely in the present subjects points to a microcirculatory rather than a macrocirculatory effect.
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PMID:Effects of habitual tobacco smoking on reactive hyperemia in the human hand. 387 16

Relative rates of proportionate mortality from cancer of six sites based on total cancer deaths and the proportions expected in all towns, and from four types of cardiovascular disease based on total deaths from all causes, have been related in the 80 county boroughs of England and Wales to the sources of water supply and to the average hardness of water in the towns. The sources of water, from upland surfaces, artesian wells and rivers, were classified in eight groups, and significant associations were found for cancers of the stomach, oesophagus, prostate, male bladder and female breast, and for hypertensive and chronic rheumatic heart disease. No associations were apparent with intestinal cancer, vascular disease of the nervous system or arteriosclerotic heart disease. Hardness or softness of the water was classified in seven groups and significant associations were found for the same diseases as for source of water, none being evident for coronary disease.
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PMID:Mortality from cancer and cardiovascular diseases in the county boroughs of England and Wales classified according to the sources and hardness of their water supplies, 1958-1967. 451 76


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