Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. ZENECA ZD7288 (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride, formerly ICI D7288) is a novel sino-atrial node function modulator which selectively slows heart rate. 2. The haemodynamic effects of ZD7288 (0.1, 0.3 and 1.0 mg kg-1, i.v.) have been evaluated and compared with those of placebo (physiological saline), zatebradine (ULFS 49, 0.1, 0.3 and 1.0 mg kg-1, i.v.) and propanolol (0.03, 0.1, and 0.3 mg kg-1, i.v.) in beagles chronically instrumented for measurement of heart rate, aortic pressure, aortic flow and dPLV/dtmax. The dogs were trained to run at 6.5 k h-1 on a level treadmill for 5 min at half hourly intervals over a period of 4 h. Drugs were dosed cumulatively after the second, fourth and sixth exercise periods. 3. Control experiments demonstrated a degree of accommodation to repeated exercise over a period of 4 h. Resting heart rate decreased by 21 beats min-1, but heart rate response to exercise was maintained, whereas dPLV/dtmax at rest remained steady while the response to exercise decreased significantly (by 25% after 2 h, P < 0.05). 4. ZD7288 and zatebradine both decreased heart rate during exercise in a dose-dependent manner, whilst heart rate at rest did not differ from resting heart rates in saline dosed control animals. In contrast, heart rate at rest and during exercise were lowered equally by the lowest doses of propranolol (approximately by 30 beats min-1), and additional doses caused only minor additional decreases. The exercise-induced tachycardia was maintained within 12% of pre-dose levels, presumably by withdrawal of vagal tone.5. Cardiac inotropism, as indicated by dPLv/dt max, was not affected by ZD7288 or zatebradine at rest,although the inotropic response to exercise decreased in proportion to the decreases in exercise-induced tachycardia. Propranolol caused a marked dose-dependent decrease in the exercise-induced inotropic response (by 85% at 0.3mg kg-1).6. Whilst the sino-atrial node modulators increased stroke volume at rest, and augmented increases in response to exercise, propranolol did not affect resting stroke volume and decreased the responses to exercise.7. Cardiac output at rest and cardiac output increases during exercise were well maintained in the presence of ZD7288 and zatebradine in contrast to propranolol which induced a significant depression of cardiac output, both at rest and during exercise. Propranolol also caused significant systemic vasoconstriction.8. In conclusion, ZD7288 has haemodynamic actions comparable to those of zatebradine despite their chemical dissimilarity. ZD7288 may be of benefit in the treatment of ischaemic heart disease by reducing heart rate without impairing cardiac function.
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PMID:The haemodynamic actions of ZENECA ZD7288, a novel sino-atrial node function modulator, in the exercising beagle: a comparison with zatebradine and propranolol. 785 51

The cardiovascular response to beta-adrenergic stimulation is markedly blunted with advancing age, and this blunting may underlie some of the prominent age-associated changes in the hemodynamic profile during dynamic exercise. To examine this hypothesis, we administered the nonselective beta-adrenergic receptor blocker propranolol (0.15 mg/kg IV) to 25 healthy normotensive men ages 28 to 72 years from the Baltimore Longitudinal Study of Aging (BLSA) immediately before maximal upright cycle ergometry with 99mTc gated cardiac blood pool scintigraphy. Their hemodynamic responses to exercise were compared with those of 70 age-matched healthy unmedicated male BLSA control subjects. The maximal cycle work rate achieved was similar in propranolol-treated men (158 +/- 32 W) and control subjects (148 +/- 32 W) and declined similarly with age in both groups. Hemodynamics at seated rest were not age-related in either group; however, propranolol-treated men had lower heart rates (HR), systolic blood pressure (SBP), ejection fraction, and cardiac index than control subjects but higher end-diastolic volume index (EDVI) and end-systolic volume index (ESVI) by covariance analysis. At maximal effort, several striking age-drug interactions were evident: Propranolol caused a greater reduction in HR and greater increases in EDVI and stroke volume index (SVI) in younger than in older men. Hence, at maximal work rate, HR declined less with age in the propranolol group (0.46 versus 1.09 beats per minute per year, P < .05 by covariance analysis); EDVI and SVI decreased with age (0.27 and 0.48 mL/m2 per year, respectively) after propranolol compared with increases of 0.47 and 0.16 mL/m2 per year in control subjects, respectively, each P < or = .05 by covariance analysis. The left ventricular contractility index, SBP/ESVI, at exhaustion was reduced by propranolol to a greater extent in younger than older men. Thus, acute beta-adrenergic blockade reverses the age-associated ventricular dilation at end diastole and end systole observed during upright cycle exercise and blunts the decline in maximal HR and myocardial contractility. These data suggest that the age-associated declines in maximal HR and left ventricular contractility during vigorous exercise are manifestations of reduced beta-adrenergic responsivity with advancing age which is partially offset by exercise-induced ventricular dilation.
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PMID:Effects of acute beta-adrenergic receptor blockade on age-associated changes in cardiovascular performance during dynamic exercise. 795 91

The aim of the study was to investigate the combined influence of thiopental and antiarrhythmic drugs: procainamide, N-acetylprocainamide, verapamil or propranolol on hemodynamic parameters in rabbits: arterial blood pressure, heart rate, cardiac output, stroke volume, peripheral vascular resistance, renal and hepatic blood flows. Propranolol used during thiopental anesthesia deepened the decrease of hepatic and renal blood flow resulting from the action of the anesthetic drug. Verapamil in a dose that did not change hepatic blood flow caused significant decrease of that parameter during thiopental anesthesia. Other hemodynamic changes observed after administration of antiarrhythmic drugs during thiopental anesthesia are essentially similar to those resulting from the action of antiarrhythmic drugs alone. The administration of procainamide or N-acetylprocainamide during thiopental anaesthesia in rabbits had no significant influence on hemodynamic changes evoked by thiopental alone. Verapamil injected to rabbits together with thiopental caused a significant decrease of blood flow in the liver, which was not observed after thiopental alone or verapamil alone. Propranolol injection together with thiopental caused a decrease of blood pressure, heart rate, cardiac output but an increase of vascular peripheral resistance, which was similar to the action of propranolol alone. Propranolol administered during thiopental anesthesia caused a significant decrease of the renal and hepatic blood flow, more marked than after the injection of that beta-blocker alone.
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PMID:The influence of selected antiarrhythmic drugs on the hemodynamic parameters in rabbits during anesthesia. Part II. Thiopental anesthesia. 868 88

Cardiac arrhythmia can be a serious complication during general anesthesia. On the other hand, there is a need for general anesthesia of patients suffering from cardiac arrhythmias and using antiarrhythmic drugs. The aim of the present experiments was to establish the way in which procainamide, N-acetyl-procainamide, verapamil and propranolol influence hemodynamic parameters of rabbits during propofol anesthesia. The experiments were performed on rabbits. Heart rate was counted from ECG. Blood pressure was measured directly in the carotid artery. Cardiac output, stroke volume, and total peripheral resistance were estimated using the method of human Cr51 albumin dilution. Hepatic blood flow was estimated after single injection of 99mTc/Sn Hepida. Renal blood flow was estimated after a single injection of 125J-hippurate. Propofol decreases renal and hepatic blood flows, decreases blood pressure and peripheral vascular resistance. Propranolol given alone or in combination with propofol decreases hepatic blood flow. The administration of antiarrhythmic drugs during propofol anesthesia decreases renal blood flow. Propofol decreases blood pressure in rabbits as a result of decreased peripheral vascular resistance. It also decreased RBF and HBF. Disadvantages of interactions of propofol and antiarrhythmic drugs concern mainly with RBF and HBF. Propranolol (given alone or in combination with propofol) strongly decreases HBF. NAPA given during P anesthesia exerts a weaker effect on HBF. The administration of antiarrhythmic drugs during propofol anesthesia decreases RBF. The strongest disadvantageous action is exerted by propranolol, the slightest one--by verapamil.
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PMID:The influence of selected antiarrhythmic drugs on the hemodynamic parameters in rabbits during anesthesia. Part I. Propofol anesthesia. 868 87

The influence of procainamide, N-acetylprocainamide, verapamil or propranolol on hemodynamic parameters in rabbits was studied during ketamine anesthesia. Using radioisotopic methods the following parameters were estimated: cardiac output, stroke volume, total peripheral resistance, renal and hepatic blood flows, arterial pressure and heart rate. During ketamine anesthesia the inhibitory effect of verapamil on peripheral resistance was intensified; after administration of the rest of antiarrhythmic drugs the decrease of peripheral resistance was not observed in the animals without general anesthesia. During ketamine anesthesia the negative chronotropic effect of N-acetylprocainamide was decreased, but the negative chronotropic effect of procainamide was intensified. Procainamide administration during ketamine anesthesia markedly decreased renal blood flow. Propranolol given without anesthetic, as well as given together with ketamine markedly decreased hepatic blood flow.
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PMID:Influence of selected antiarrhythmic drugs on the hemodynamic parameters in rabbits during anesthesia. Part III. Ketamine anesthesia. 886 32

1. Cardiovascular effects of centrally administered endothelin-1 (ET-1) were studied in control and propranolol-treated anesthetized rats using a radioactive microsphere technique. 2. In the control group, blood pressure, cardiac output, and stroke volume were decreased, and heart rate was not altered after the administration of ET-1.ET-1 produced a reduction in blood flow to the brain, heart, kidneys, gastrointestinal tract, portal system, musculoskeletal system, and skin. 3. Propranolol significantly attenuated the decrease in blood pressure, cardiac output and stroke volume induced by centrally administered ET-1. The reduction in blood flow to the brain, heart, kidneys, gastrointestinal tract, portal system, musculoskeletal system and skin induced by centrally administered ET-1 was blocked by propranolol. 4. It is concluded that centrally administered ET produces significant cardiovascular effects which are mediated through the sympathetic nervous system and could be antagonized by propranolol. These findings can also be helpful in explaining some of the beneficial effects of propranolol in various cardiovascular disorders involving central ET mechanisms.
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PMID:Modification of systemic and regional circulatory effects of intracerebroventricular administration of endothelin-1 by propranolol in anesthetized rats. 890 86

Exertion symptoms occur frequently in subjects with hyperthyroidism. Using stress echocardiography, exercise capacity and global left ventricular function can be assessed noninvasively. To evaluate stress-induced changes in cardiovascular function, 42 patients with untreated thyrotoxicosis were examined using exercise echocardiography. Studies were performed during hyperthyroidism, after treatment with propranolol, and after restoration of euthyroidism. Twenty-two healthy subjects served as controls. Ergometry was performed with patients in a semisupine position using a continuous ramp protocol starting at 20 watts/min. In contrast to control and euthyroidism, the change in end-systolic volume index from rest to maximal exercise was lower in hyperthyroidism. At rest, the stroke volume index, ejection fraction, and cardiac index were significantly increased in hyperthyroidism, but exhibited a blunted response to exercise, which normalized after restoration of euthyroidism. Propranolol treatment also led to a significant increase of delta (delta) stroke volume index. Maximal work load and delta heart rate were markedly lower in hyper- vs. euthyroidism. Compared to the control value, systemic vascular resistance was lowered by 36% in hyperthyroidism at rest, but no further decline was noted at maximal exercise. The delta stroke volume index, delta ejection fraction, delta heart rate, and maximal work load were significantly reduced in severe hyperthyroidism. Negative correlations between free T3 and diastolic blood pressure, maximal work load, delta heart rate, and delta ejection fraction were noted. Thus, in hyperthyroidism, stress echocardiography revealed impaired chronotropic, contractile, and vasodilatatory cardiovascular reserves, which were reversible when euthyroidism was restored.
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PMID:Stress echocardiography in hyperthyroidism. 1040 94

Effects of isoproterenol on contraction and membrane potential of gastric smooth muscle were studied in stroke prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar Kyoto rats (WKY). Circular muscle preparation from the gastric fundus developed tonic contraction by re administration of Ca2+ to a nominally Ca2+-free solution. The contraction was inhibited by nifedipine or nicardipine. Isoproterenol induced relaxation when it was applied to the Ca2+-induced contraction. The amplitude of isoproterenol induced relaxation was concentration-dependent. Propranolol 10(-6) M abolished the relaxation induced by isoproterenol 10(-7) M. In the preparation from SHRSP, the amplitude of isoproterenol induced relaxation was smaller than that from WKY between 3 x 10(-9) and 10(-7) M. Forskolin, an adenylate cyclase activator, induced concentration-dependent relaxation. There was no difference in the relaxation induced by forskolin between preparations from WKY and SHRSP. Dibutilyl cyclic AMP, a membrane permeable analogue of cyclic AMP, also induced similar relaxation in preparations from WKY and SHRSP. Resting membrane potential of smooth muscle cell was not different between preparations from WKY and SHRSP. Isoproterenol hyperpolarized the membrane concentration-dependently. Isoproterenol-induced hyperpolarization in the preparation from SHRSP was smaller than that from WKY between 10(-8) and 10(-6) M. When the membrane was depolarized by Tyrode's solution containing 40 mM K+, isoproterenol-induced hyperpolarization was almost abolished. In this condition, the isoproterenol-induced relaxation was inhibited partly, however, there was no difference in the amplitude of relaxation between preparations from WKY and SHRSP. Therefore, isoproterenol-induced hyperpolarization contributed at least partly to the relaxation. Forskolin hyperpolarized the membrane by the same amplitude in the preparations from WKY and SHRSP. These results indicate that a decrease in hyperpolarization may contribute to the decreased relaxation by isoproterenol in the preparation from SHRSP.
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PMID:Altered beta-adrenoceptor-mediated responses in the gastric smooth muscle of hypertensive rats. 1083 Apr 73

Cardiovascular responses during a graded lower body negative pressure (LBNP) protocol were compared before and after atropine and propranolol administration to test the hypothesis that both sympathetic and parasympathetic control of cardio-acceleration are associated with syncopal predisposition to orthostatic stress in healthy subjects. Eleven men were categorized into two groups having high (HT, N = 6) or low (LT, N = 5) tolerance based on their total time before the onset of presyncopal symptoms. HT and LT groups were similar in physical characteristics, fitness, and baseline cardiovascular measurements. Atropine treatment had no effect on LBNP tolerance or mean arterial pressure at presyncope, despite an atropine-induced increase in heart rate. Propranolol treatment reduced (p<0.05) LBNP tolerance in both groups. Diminished LBNP tolerance after propranolol administration was associated with reductions in cardiac output, whereas increase in systemic peripheral resistance from baseline to presyncope was unaffected by propranolol. Reduction in cardiac output and LBNP tolerance after beta blockade reflected a chronotropic effect because lower LBNP tolerance for the HT (-50%) and LT (-39%) groups was associated with dramatic reductions (p <0.05) in the magnitude of LBNP-induced tachycardia without significant effects on stroke volume at presyncope. Absence of an atropine-induced difference in cardiac output and systemic peripheral resistance between HT and LT groups failed to support the notion that cardiac vagal withdrawal represents a predominant mechanism that could account for differences in orthostatic tolerance. Because a reduction in LBNP tolerance in both HT and LT groups after propranolol treatment was most closely associated with reduced tachycardia, the data suggest that a primary autonomically mediated mechanism for maintenance of mean arterial pressure and orthostatic tolerance in healthy subjects is beta adrenergic-induced tachycardia.
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PMID:Effects of cholinergic and beta-adrenergic blockade on orthostatic tolerance in healthy subjects. 1132 87

We examined the effects of the angiotensin-converting enzyme inhibitor perindopril and the beta-blocker propranolol on dilator responses of cerebral arterioles in chronic hypertension. Dilator responses to acute hypotension were examined in untreated Wistar-Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) that were untreated or treated for 3 months with a low (0.3 mg. kg(-1). day(-1)) or a high (2 mg. kg(-1). day(-1)) dose of perindopril or a dose of propranolol (250 mg. kg(-1). day(-1)) alone or in combination with the low dose of perindopril. Pressure (servo-null) and diameter were measured in cerebral arterioles during acute reductions in arterial pressure both before and during maximal dilatation (EDTA). The high dose of perindopril or the combination of propranolol and perindopril normalized cerebral arteriolar pressure (52+/-2 [mean+/-SEM], 49+/-2 mm Hg versus 50+/-2 mm Hg in WKY and 96+/-3 mm Hg in untreated SHRSP; P<0.05). In contrast, the low dose of perindopril or propranolol alone did not normalize arteriolar pressure (74+/-2 mm Hg and 58+/-3 mm Hg). Both the low and high doses of perindopril improved autoregulatory dilatation, maximal dilatation, and dilator reserve of cerebral arterioles in SHRSP, with the low dose of perindopril being almost as effective as the high dose of perindopril. Propranolol alone did not significantly improve dilator function of cerebral arterioles. Furthermore, dilator function of cerebral arterioles was not further improved by the addition of propranolol to the low dose of perindopril. These findings suggest that angiotensin-converting enzyme inhibitors, such as perindopril, may be more effective than propranolol in attenuating the impairment of cerebral autoregulatory vasodilatation, maximal dilatation, and dilator reserve during treatment of chronic hypertension.
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PMID:Effects of an angiotensin-converting enzyme inhibitor and a beta-blocker on cerebral arteriolar dilatation in hypertensive rats. 1140 82


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