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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study compares the effects of Ro 31-6930, a novel potassium channel opener, with those of cromakalim and nitrendipine on blood pressure and other haemodynamic parameters. In conscious, spontaneously hypertensive rats (SHR) the oral dose of Ro 31-6930 for lowering blood pressure was 10 times lower than that of cromakalim and some 100 times lower than that of nitrendipine. In addition, the duration of antihypertensive activity of Ro 31-6930 was longer than that of cromakalim or nitrendipine. The tachycardia evoked by Ro 31-6930 and cromakalim was of shorter duration than the antihypertensive effect of either agent. In a repeat, once daily dosing experiment no tolerance was observed to the antihypertensive effect of Ro 31-6930 over a 22-day period. In conscious normotensive cats Ro 31-6930 was 10 times more potent than cromakalim and 1,000 times more potent than nitrendipine in reducing blood pressure. The duration of hypotensive activity was in excess of 5 h for each agent. In anaesthetised dogs all three agents reduced mean arterial pressure (MAP) and total peripheral resistance (TPR), while increasing cardiac output (CO) via a rise in stroke volume (SV). Both Ro 31-6930 and cromakalim significantly reduced femoral (FVR) and mesenteric vascular resistances (MVR), while only cromakalim reduced renal vascular resistance (RVR). Ro 31-6930 is a potent new antihypertensive agent that compares favourably with cromakalim and nitrendipine.
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PMID:Preclinical pharmacology of Ro 31-6930, a new potassium channel opener. 168 12

Focal cerebral ischemia was produced by occluding the left middle cerebral artery in 769 rats. Permeability of the blood-brain barrier to small or large molecules was evaluated qualitatively using Evans blue or sodium fluorescein and quantitatively using the transfer indexes of iodine-125-labeled bovine serum albumin or [14C]sucrose. Water content was determined using wet and dry weights and sodium and potassium contents using flame photometry. Cortical tissue in the middle cerebral artery territory was sampled less than or equal to 14 days after occlusion. A significant increase in the albumin transfer index was first found 12 hours after occlusion, and the index remained approximately the same until water content peaked 3 days after occlusion. In contrast, the sucrose transfer index increased gradually, significantly correlated with increases in the water and sodium contents. Tissue staining by sodium fluorescein was more extensive than that by Evans blue. As edema fluid decreased gradually 4-10 days after occlusion, the albumin and sucrose transfer indexes increased markedly. These findings indicate that disruption of the blood-brain barrier to small molecules is accompanied by accumulation of edema fluid during the later stages of ischemia. Opening of the barrier to serum protein is probably related to the resolution of edema.
Stroke 1990 Apr
PMID:Brain edema and cerebrovascular permeability during cerebral ischemia in rats. 169 34

These experiments compared potential-operated calcium channel function in smooth muscle from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY). Carotid artery strips from adult male SHRSP and WKY rats were suspended in tissue baths for isometric force recording. Contractile force was expressed as percent of response to 100 mmol/l KCl. Vascular strips from SHRSP were more sensitive to KCl (ED50 = 25 mmol/l) compared to strips from WKY rats (ED50 = 37 mmol/l). The calcium channel agonist Bay K 8644 (2.8 x 10(-10) to 2.8 x 10(-7) mol/l) produced tonic contractions in carotid artery strips from SHRSP (34% of the contractile response to 100 mmol/l KCl) but not in those from WKY rats. Incubation of vascular strips in 1.8 or 6 x 10(-10) mmols/l norepinephrine did not alter the maximal contractile response to Bay K 8644 in either strain of rats. In 12 mmol/l KCl, the maximal contractile response to Bay K 8644 was increased in both SHRSP (71%) and WKY rats (25%). In 18 mmol/l KCl, maximal contractile responses to Bay K 8644 in the two strains were similar (SHRSP = 73%, WKY = 76%). Removal of the endothelium did not significantly affect contractile responses to Bay K 8644 in either strain of rats. There were no differences in contractile responses to the calcium ionophore A23187 or in nifedipine-induced relaxation of potassium-activated vessels between carotid arteries from SHRSP and WKY rats. In summary, these results suggest that a difference in voltage-operated calcium channel function may underlie the increased sensitivity of SHRSP vascular smooth muscle to depolarizing stimuli.
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PMID:Increased vascular reactivity to Bay K 8644 in genetic hypertension. 170 Apr 45

We examined the specific hypotheses linking the intake of sodium, potassium, calcium, magnesium, and protein to blood pressure (BP) and the relationship between dietary factors and mortality from the major cardiovascular diseases (CVD) in the Ecuadorian populations. Two Ecuadorian populations, the urban and the rural, were selected from Quito and Vilcabamba, respectively. From Quito: 87 men and 83 women; from Vilcabamba: 71 men and 91 women aged 50-54 were randomly selected for BP measurement, 24-h urine collection, and blood sampling according to the Cardiovascular Disease and Alimentary Comparison (CARDIAC) Study protocol. Samples were analyzed at CARDIAC center in Izumo, Japan. Mean systolic blood pressure (SBP) was not much different in the two populations, but mean diastolic blood pressure (DBP) and body mass index (BMI) were significantly lower in Vilcabamba (p less than 0.001). Mortality from stroke was higher in Vilcabamba, whereas coronary death rate was higher in Quito. Both sodium intake and sodium/potassium ratio were higher in Vilcabamba (p less than 0.001). Protein intake and serum cholesterol were higher in Quito (p less than 0.001). Urinary taurine excretion was higher in Quito. There was no difference in W3/W6 fatty acids ratio between the two populations. Multiple regression analyses of intracommunity correlation indicated that both SBP and DBP were highly significantly related with BMI in Quito and that urinary excretions were inversely related to SBP. Serum cholesterol was positively related to coronary death rate. Mortality from stroke was inversely related to both serum cholesterol and protein and was positively related to salt consumption.
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PMID:Cardiovascular risk factors in two Ecuadorian urban and rural populations. The Ecuadorian-Japan Cooperative CARDIAC Study Group. 170 22

The development of genetic rat models for research on hypertension, stroke and other cardiovascular diseases (CVD) such as spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) have contributed not only to the elucidation of the pathogenesis of hypertension-related CVD but also to their prediction and prevention. Since both genetic and environmental factors are involved in the pathogenesis of CVD as extensively studied so far on these models, the detection of the early pathogenic mechanisms related to the genetic factors and the control of environmental factors such as dietary improvement are useful as predictive and preventive measures against CVD. Sympathetic overresponsiveness, early development of cardiovascular hypertrophy, increased salt sensitivity and membrane or transport abnormalities in vascular smooth muscle cells (VSMC) from SHR and SHRSP, possibly related to the pathogenesis of hypertension, are so far regarded as predictors for hypertension partly applicable to human hypertension. Genetic pathogenic mechanisms of stroke in SHRSP which have been proven to be greatly influenced also by dietary factors are hypertension-induced VSMC degeneration and necrosis of intracerebral arteries due to local nutritional disturbance. One of predictors of stroke related to the pathogenic mechanisms is reduction of regional cerebral blood flow. On the other hand, the control of environmental factors, especially nutrition and diets such as intakes of animal and vegetable proteins, some amino acids and fatty acids, potassium, calcium, magnesium, dietary fibers, etc., have been experimentally demonstrated to be effective for the prevention of CVD in these genetic models, and the applicability of these experimental findings to the CVD prevention in man is now supported from our world-wide epidemiological studies (WHO CARDIAC Study).
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PMID:Overview: studies on spontaneous hypertension-development from animal models toward man. 177 99

The most common cause of death in hypertensive patients is myocardial infarction (MI), being three times more common than stroke. Lowering raised BP results in 40% fewer strokes, but only 14% fewer MIs. This may be because other coronary risk factors that often accompany hypertension (e.g. obesity, lipid and thrombotic disturbances, insulin insensitivity, increased plasma renin activity and increased sympathetic activity) are either unaffected or exacerbated by some of the traditional antihypertensive agents. Some of these risk factors show a diurnal rhythm peaking at 07.00-10.00 hours, thus this time constitutes a 'vulnerable period' for sudden death or death from MI. beta-blockers and diuretics have been effective in preventing stroke, but diuretics (at least potassium-losing diuretics) might actually increase the incidence of sudden death and MI in young to middle-aged hypertensive subjects (though elderly patients may benefit). Quality of life can be impaired by some beta-blockers, and diuretics can cause metabolic upset and male impotence. Thus, antihypertensive agents that are not only effective and well tolerated but are beneficial to the broader coronary risk profile are desirable. ACE inhibitors should prove particularly useful in terms of: good quality of life; non-exacerbation or improvement of coronary risk factors; treating patients with impaired left ventricular function; reversing left ventricular hypertrophy and vascular wall hypertrophy, thus improving coronary flow reserve; atheroma regression; renal protection, particularly in diabetes; and prevention or regression of LV dilatation (remodelling) following MI.
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PMID:What does the future hold for ACE inhibitors? 179 18

We examined the effect of atrial natriuretic peptide on cerebral edema in 96 rats. Forty-four rats were given 30 (n = 11), 120 (n = 26), or 150 (n = 7) micrograms/kg of the peptide intravenously over 24 hours after occlusion of the left middle cerebral artery to induce cerebral ischemia. We then measured the brain water content, the brain sodium and potassium contents, the in vitro proton nuclear magnetic resonance longitudinal (T1) and transverse (T2) relaxation times, and the area of the edematous regions. Compared with saline treatment (n = 39), peptide treatment decreased the brain water content in a dose-dependent manner and decreased the brain sodium content significantly (p less than 0.05). Peptide treatment also suppressed the lengthening of both T1 and T2 in edematous tissue (p less than 0.05 and p less than 0.01, respectively) and reduced the area of the edematous regions observed by magnetic resonance imaging (p less than 0.01). Atrial natriuretic peptide appears to have a pharmacological effect on ischemic brain edema, possibly by suppressing the elevation of water content through regulation of electrolyte transport in the brain.
Stroke 1991 Jan
PMID:Effects of atrial natriuretic peptide on ischemic brain edema in rats evaluated by proton magnetic resonance method. 182 2

The present study compares simple hypothermic storage and hypothermic perfusion in a swine model of heart transplantation using metabolic and functional assessments. In both groups the hearts were initially protected with iso-osmolar potassium Tyers' cardioplegia. The donor hearts of group A were placed in simple hypothermic storage for 5 h. The donor hearts of group B were placed onto a perfusion apparatus for 5 h with perfusion pressure maintained at 28 cm of H2O and a myocardial temperature of 8-10 degrees C. The perfustate consisted of Tyers' solution with the addition of 2 mg/L of mannitol, 12.5 mg/L of glucose, 5 units/L of insulin, and 95% oxygen. The ischemic interval within both groups was 6 h, including orthotoipic transplantation. Investigation was conducted at three time periods: prepreservation (T1) in the donor, and postpreservation (T2) and immediately after loading (T3) in the recipient. Following volume loading for the hypothermic perfusion group there was significant improvement of myocardial function (cardiac index, p less than .05; stroke index, p less than .05) with no significant change in systemic vascular resistance, systemic blood pressure, and heart rate. There was also significant improvement in myocardial performance (p less than .05) for the hypothermic perfusion group following volume loading. Results of fatty acid turnover using 15-p-iodo (123I)-phenylpentodecanoic acid indicate significantly greater increase in metabolic rate for the perfusion group than for the hypothermic storage group. (p less than .05). This indicates improved metabolic status of the heart treated with the hypothermic perfusion technique. We conclude that a combination of functional and metabolic assessments is a good method for deduction of ischemic-reperfusion injury. We also conclude that hypothermic perfusion is superior to hypothermic storage for in vitro preservation of hearts for heart transplantation.
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PMID:Comparison of functional and metabolic assessments in preservation techniques for heart transplantation. 186 92

The effects of moderate, chronic (5 days) potassium depletion on cardiac function were assessed in 14 normokalemic and 13 hypokalemic open chest, anesthetized dogs. Cardiac responses to intravenous bolus injection of 2.5 micrograms/kg body weight epinephrine (10 normokalemic and 11 hypokalemic dogs) and to rapidly increased preload (8 dogs in each group) were evaluated. Hypokalemic dogs received a low potassium diet plus chlorthalidone. Plasma potassium levels were lower (p less than 0.001) in the hypokalemic dogs (3.2 +/- 0.1 mEq/liter [mean +/- SEM]) than in the normokalemic dogs (4.1 +/- 0.1). The inotropic response to epinephrine was lower in hypokalemic than in normokalemic dogs, the response of the maximal rate of rise of left ventricular pressure was 20% greater (p less than 0.03) and the response of the peak rate of change of ejection power was 60% greater in the normokalemic dogs. The relaxation response to epinephrine (the maximal rate of fall of left ventricular pressure) was 33% lower (p less than 0.02) in hypokalemic dogs. Responses to rapid volume expansion were impaired by hypokalemia; maximal stroke volume index was 31% lower (p less than 0.01), maximal cardiac index was 26% lower (p less than 0.01) and the peak response to the maximal rate of filling was 51% lower (p less than 0.01). There were no differences in basal cardiac function. Therefore, modest potassium depletion within the clinical range impaired the contractile and relaxation responses to epinephrine and preload and impaired rapid filling.
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PMID:Chronic hypokalemia and the left ventricular responses to epinephrine and preload. 189 55

The electrophysiological actions of TRH were examined in the clonal pituitary cell line GH3 with the use of the perforated patch variation of the standard whole cell patch-clamp technique. The action of TRH on spontaneously spiking cells was to cause a brief hyperpolarization (first phase action), followed by a period during which action potential behavior was significantly modified (second phase action). The modifications during second phase action included a reduction in the slope of the up-stroke, a reduced peak potential, an increase in duration, and a depolarizing shift of the after-hyperpolarization. The modification of voltage- and calcium-dependent conductances that underlie these changes were investigated in voltage clamp experiments. During first phase action TRH was found to increase calcium-dependent potassium current. During second phase action TRH was found to significantly reduce the L-type calcium current (35%), with no alteration in the T-type calcium current. The second phase action of TRH on calcium-dependent potassium conductance was complex. First, a decrease was observed. This was followed by an increase that did not become fully manifest until after TRH was washed from the cell. TRH caused no change in voltage-dependent potassium current. These results indicate that the second phase action of TRH on action potential behavior in GH3 cells is mediated by a reduction in L-type calcium current and alterations in the behavior of calcium-dependent potassium currents, but not through changes in voltage-dependent potassium currents.
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PMID:Reevaluation of the electrophysiological actions of thyrotropin-releasing hormone in a rat pituitary cell line (GH3). 190 Jul 83


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