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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical use of the immunosuppressant cyclosporine A (CyA) is associated with nephrotoxicity and hypertension of unknown mechanisms. Because the vascular endothelium is now known to influence vascular tone by release of relaxing factors and CyA can damage endothelial cells, it was of interest to determine if CyA could induce a rise in blood pressure (BP) in normal rats and if this was associated with increased vascular responses to constrictor stimuli and/or decreased responses to endothelium-dependent dilators. Male Wistar rats were treated daily for 21 days by gavage with 5, 10 or 20 mg/kg of CyA or olive oil vehicle (1 ml/kg). Creatinine clearance was measured before treatment and on day 19. On day 20 the rats were anesthetized with ether and a carotid artery cannulated and exteriorized. On day 21 mean arterial BP and heart rate were recorded directly for 1 hr while the rats were conscious and unrestrained. An arterial blood sample was taken for analysis of catecholamines by high-performance liquid chromatography. The rats were then anesthetized and both kidneys isolated and perfused at 3 ml/min with Krebs' solution. Vasoconstrictor responses were obtained to periarterial renal nerve stimulation (1-30 Hz) and to bolus injections of norepinephrine (10-300 ng), angiotensin II (1-30 ng) and potassium (30-100 mumol). Perfusion pressure was then increased by 125 mm Hg with a norepinephrine infusion and vasodilator responses obtained to the incremental infusion of acetylcholine (1 nM-1 microM) and nitroprusside (100 nM-3 microM). CyA treatment decreased creatinine clearance and produced a dose-dependent increase in BP and heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclosporine treatment of normal rats produces a rise in blood pressure and decreased renal vascular responses to nerve stimulation, vasoconstrictors and endothelium-dependent dilators. 278 81

Recent investigations suggest angiotensin converting enzyme (ACE) activity is generally decreased in normotensive pregnancy, but less is known about the level of activity of this enzyme in hypertensive pregnant subjects. The primary source of ACE is vascular endothelium and it can be measured in serum or plasma. In a preliminary investigation, we measured and compared diastolic blood pressure and serum ACE activity in 14 uncomplicated pregnant subjects during the third trimester, and in 16 subjects of similar gestation duration hospitalized with pregnancy-induced hypertension PIH. No patient had a positive history for, or evidence of, pulmonary or other metabolic disease. Compared with levels in normal pregnancy, serum ACE activity was found to be significantly elevated in PIH. In this study, this increase was not due to differences between the groups in maternal chronologic age or gestational duration. Further studies are necessary to determine if the increase in ACE activity precedes or follows development of clinically apparent PIH. If the former is the case, ACE activity might be a useful indicator of risk for PIH.
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PMID:Angiotensin converting enzyme activity in hypertensive pregnancy. 282 97

These recommendations for secondary prevention of clinical coronary cardiopathy are the result of a symposium attended by 46 experts belonging to the councils on arteriosclerosis, clinical cardiology, epidemiology, and prevention and rehabilitation of the International Society and Federation of Cardiology. Secondary prevention of coronary cardiopathy refers to measures designed to prevent deterioration or death in patients with clinical manifestations of coronary cardiopathy. Such measures in addition to drugs include health actions that may improve the status of various coronary risk factors: the patient's life style should stress maintenance of proper weight, regular physical exercise, reduction of saturated fats and cholesterol in the diet, and elimination of smoking and excessive alcohol consumption. It is considered reasonable to control hypertension through the most innocuous means possible, but findings of the few existing controlled studies of effects of treatment of hypertension in coronary cardiopathy are complex. Drug treatment may be necessary for most patients, but nondrug measures should be added when possible. Various proofs including results of some controlled studies justify the recommendations for reducing elevated levels of serum cholesterol and low density lipoprotein cholesterol through dietary measures. Optimum plasma cholesterol levels are 5.2 mmol/1 or less, and the upper limit is 5.7 mmol/1. The rules for secondary prevention are the same for diabetics as for nondiabetics, but some special precautions are necessary in diabetics. Habitual and vigorous physical activity has been associated with a decline in the incidence of coronary cardiopathy in different population studies, although there has been no demonstration that exercise can alter the progression of atherosclerosis or improve collateral circulation. Stress should be recognized as a risk factor and included in secondary prevention, but the concept that stress is the key risk factor in coronary events is in conflict with a large body of scientific evidence. Oral contraceptives (OCs) tend to increase boood pressure and weight as well as serum triglyceride levels, and to reduce glucose tolerance and high density lipoprotein cholesterol in some formulations. OCs also affect the integrity of the vascular endothelium and alter blood coagulation, fibrinolysis, and platelet function. These thrombogenic changes are intensified with age, especially after 35, and with smoking. OCs are innocuous in women under 35 with no history of venous or arterial disease or pulmonary embolism and who have normal blood pressure and serum cholesterol levels. Patients using OCs should control their blood pressure and weight and be alert to any symptoms of thrombotic episodes. The risk/benefit ratio of longterm estrogen treatment in meno- and postmenopausal women with coronary cardiopathy has not yet been established. Apart from 1 study in primates, there is no evidence that vasectomy should be considered either indicated or contraindicated for coronary patients. Beta blockers, platelet function inhibitors, anticoagulants, and other drugs are under active study for secondary prevention of coronary cardiopathy.
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PMID:[Recommendations for secondary prevention of the clinical coronary cardiopathy]. 285 11

The biochemical mechanism of action of synthetic atrial natriuretic factor (atriopeptin II) was studied in vascular smooth muscle of the rabbit thoracic aorta. Atriopeptin II caused a time-dependent and concentration-dependent increase in tissue levels of cyclic guanosine monophosphate that corresponded in these same tissues with vascular relaxation. The elevation of arterial cyclic guanosine monophosphate levels preceded the onset of vascular relaxation. Atriopeptin II did not alter vascular levels of cyclic adenosine monophosphate. The presence of a functionally intact vascular endothelium was not necessary for atriopeptin II to elicit vascular relaxation. Atriopeptin II-induced vascular relaxation and elevation of cyclic guanosine monophosphate levels were inhibited by the guanylate cyclase inhibitor methylene blue. These data suggest cyclic guanosine monophosphate mediates vascular relaxation produced by atriopeptin II.
Hypertension
PMID:Cyclic guanosine monophosphate mediates vascular relaxation induced by atrial natriuretic factor. 298 20

Local tissue renin-angiotensin systems have recently been discovered in various organs, and evidence is accumulating that inhibition of these local renin-angiotensin systems may contribute to the actions of converting enzyme (CE) inhibitors. Measurements of CE activity and angiotensin II concentrations revealed that after oral administration of CE inhibitors, CE was inhibited not only in lung vascular endothelium and blood, but also in the heart, kidney, vascular wall, brain and other organs. The functional significance of tissue CE inhibition is suggested first by the antihypertensive effect of brain CE inhibition in spontaneously hypertensive rats, second by the concomitant persistence of blood pressure decrease and CE inhibition in vascular wall and kidney after long-term oral CE inhibitor treatment and third by ex vivo experiments demonstrating marked effects of oral CE inhibitor pretreatment on cardiac function in isolated rat hearts. Local inhibition of tissue renin-angiotensin systems may be an important factor involved in the beneficial effects of CE inhibitors in such cardiovascular diseases as arterial hypertension, congestive heart failure and cardiac arrhythmias.
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PMID:Effect of converting enzyme inhibitors on tissue converting enzyme and angiotensin II: therapeutic implications. 303 27

Local renin-angiotensin systems have been described in organ controlling cardiovascular function. Following oral administration of converting enzyme (CE) inhibitors the enzyme was inhibited not only in lung vascular endothelium and blood, but also in the heart, kidney, vascular wall, brain and other organs. Evidence for a contribution of tissue CE inhibition to the cardiovascular actions of CE inhibitors is provided by the antihypertensive effect of brain CE inhibition in spontaneously hypertensive rats, by the concomitant persistence of blood pressure decrease and CE inhibition in vascular wall and kidney after chronic oral CE inhibitor treatment, and by the marked effects of oral CE inhibitor pretreatment on cardiac function in isolated rat hearts. Local inhibition of tissue renin-angiotensin systems may therefore be an important factor involved in the beneficial effects of CE inhibitors in cardiovascular diseases such as arterial hypertension, congestive heart failure, and cardiac arrhythmias.
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PMID:Tissue converting enzyme inhibition and cardiovascular effects of converting enzyme inhibitors. 303 5

Endothelium-derived relaxing factor (EDRF) is a labile humoral agent released by vascular endothelium that mediates the relaxation induced by some vasodilators, including acetylcholine and bradykinin. EDRF also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to vascular endothelium. These actions of EDRF are mediated through stimulation of the soluble guanylate cyclase and the consequent elevation of cyclic guanosine 3',5'-monophosphate. EDRF has been identified as nitric oxide (NO). The pharmacology of NO and EDRF is indistinguishable; furthermore, sufficient NO is released from endothelial cells to account for the biological activities of EDRF. Organic nitrates exert their vasodilator activity following conversion to NO in vascular smooth muscle cells. Thus, NO may be considered the endogenous nitrovasodilator. NO is synthesized by vascular endothelium from the terminal guanido nitrogen atom(s) of the amino acid L-arginine. This indicates the existence of an enzymic pathway in which L-arginine is the endogenous precursor for the synthesis of NO. The discovery of the release of NO by vascular endothelial cells, the biosynthetic pathway leading to its generation, and its interaction with other vasoactive substances opens up new avenues for research into the physiology and pathophysiology of the vessel wall.
Hypertension 1988 Oct
PMID:The discovery of nitric oxide as the endogenous nitrovasodilator. 304 40

Experiments were designed to investigate the importance of vascular endothelium in the vasomotor response to increases in flow as observed in conduit arteries (flow-dependent dilation). The diameter changes of femoral arteries (sonomicrometry) in response to increases in flow before and after endothelial damage procedures were studied in 23 dogs anesthetized with sodium pentobarbital. The functional integrity of the endothelial cells underneath the diameter sensors was tested by intra-arterial acetylcholine (local acetylcholine dilation) applied proximally to the sensors while a constant flow was maintained. Unilateral augmentation of femoral arterial flow (4.6 +/- 1.9-fold) induced by peripheral vasodilation or by arteriovenous shunt, elicited dilation (increase in diameter, 116 +/- 91 microns) in 18 of 23 dogs, whereas the diameter of the contralateral control artery was not affected. Mechanical removal of the endothelial cells by means of a balloon catheter abolished both the flow-dependent dilation and the local acetylcholine dilation, whereas the vasomotor responses to norepinephrine and nitroglycerin were not affected. Brief perfusions (1 minute) of the arteries with cell-free hydrogen peroxide solution (90 mM) also abolished the flow-dependent dilation and attenuated the local acetylcholine dilation (by 27 +/- 19%; p less than 0.02), while the responses to norepinephrine and nitroglycerin were not altered. These results suggest that endothelial cells act as mediators of flow-dependent dilation.
Hypertension 1986 Jan
PMID:Crucial role of endothelium in the vasodilator response to increased flow in vivo. 308 Mar 70

Cardiopulmonary bypass in children with congenital heart disease is associated with significant morbidity manifested by increased complement degradation products, heightened pulmonary vascular activity, and coagulopathy. In adults with cardiac disease, the prostaglandins (eicosanoids) have been shown to contribute to the pathophysiologic response to extracorporeal circulation. This study assessed the effect of cardiopulmonary bypass in infants and children on two potent eicosanoids: thromboxane, a vasoconstrictor and platelet aggregating agent, and prostacyclin, a vasodilator and platelet disaggregating agent. The biochemical profiles of thromboxane and prostacyclin were evaluated in temporal relationship to selected parameters of platelet loss and pulmonary vascular hemodynamics during and after cardiopulmonary bypass. Twenty-one children, aged 3 days to 9 years, with congenital heart defects who were undergoing repair with cardiopulmonary bypass were studied. Nine pediatric patients undergoing palliative heart operations with no cardiopulmonary bypass served as the control group. In the group having cardiopulmonary bypass, the thromboxane concentration significantly increased during bypass (195 +/- 10 to 910 +/- 240 pg/ml, +/- standard error of the mean, p less than 0.005), whereas the control group demonstrated no significant change in thromboxane concentration. The highest thromboxane values were seen in the youngest patients (p less than 0.002). There was no significant correlation between thromboxane changes with alterations in pulmonary vascular resistance, platelet loss, duration of cardiopulmonary bypass or aortic cross-clamping. Prostacyclin levels rose significantly in both the bypass group (100 +/- 20 to 570 +/- 80 pg/ml, p less than 0.01) and in the control group (109 +/- 44 to 589 +/- 222 pg/ml, p less than 0.01), which apparently is due to surgical manipulation of vascular endothelium. These data show that eicosanoid production is significantly altered in children during cardiopulmonary bypass. Although thromboxane, a potent vasoconstrictor, is produced in significant amounts during and after cardiopulmonary bypass, our data show that thromboxane does not directly mediate changes in pulmonary artery hypertension and is not quantitatively related to platelet loss during pediatric cardiovascular operations.
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PMID:Effects of cardiopulmonary bypass on eicosanoid metabolism during pediatric cardiovascular surgery. 328 61

The morphologic findings of renal biopsies (four cases studied by electron microscopy) and renal specimens obtained from 44 autopsies of patients who died after heart transplantation are reviewed. Eight patients treated postoperatively with cyclosporine (serum concentration of 100 to 150 ng/ml), with a survival rate of 1 to 24 months, constantly had renal lesions of variable severity. Correlated with functional renal disturbances, these changes predominantly affect the proximal convoluted tubule: vacuolization, calcifications, and tubular atrophy. The interstitial fibrosis, increasing parallel to tubular alterations, occurs only after 3 months after transplantation. The hypertrophy of juxtaglomerular apparatus and the arteriolar sclerosis noted on and after the fourth month were associated with arterial hypertension. Among the other inconstant and mild lesions (attrition of vascular endothelium and arteriolar or glomerular thrombi), the partial sclerosis of glomerular flocculus, probably correlated with tubular lesions, seems more significant. Thus these findings corroborate the nephrotoxicity of cyclosporine (principally against the proximal convoluted tube), the increase of lesions with time, and the possible irreversibility of the lesions despite appropriately decreasing the dosage of cyclosporine to eliminate toxic side effects.
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PMID:Morphology of cyclosporine nephrotoxicity in human heart transplant recipients. 330 18


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