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1.
Ten milligrams nifedipine was administered orally to young and old persons with or without hypertension, and the acute effects of nifedipine on the renin-angiotensin-aldosterone system were studied one half to 3 hours later. Nifedipine reduced blood pressure and increased pulse rate in young and old persons with or without hypertension. Simultaneously, nifedipine produced a significant increase of plasma renin activity in young persons with or without hypertension but failed to do so in old persons with or without hypertension. As a result, angiotensin I and II increased significantly in young persons but not in old persons. Hydralazine elevated aldosterone concentration by stimulating the renin-angiotensin system but nifedipine failed to do so despite its effect on the renin-angiotensin system in young individuals. Since calcium is required to secrete aldosterone, it is suggested that nifedipine blocked aldosterone secretion by the agent's calcium antagonizing action. 相似文献
2.
C Lacour F Canals G Galindo P Chatelain D Nisato 《Archives des maladies du coeur et des vaisseaux》1990,83(8):1281-1284
SR 33557 (SR) is a new calcium channel blocker belonging to the chemical class of indolizinsulfones (IC50 = 0.6 nM, 3H-nitrendipine). Its hypotensive effects were studied in conscious spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, and compared to those of Nitrendipine (Nit) (IC50 = 0.8 nM, 3H-nitrendipine). SR was given intravenously (IV) at 0.3, 1 and 3 mg/kg (n = 4 to 6) and orally (PO) at 3, 10, 30 and 60 mg/kg (n = 4 to 7). Nitrendipine was studied at 0.3 mg/kg (IV) and 10 mg/kg (PO). Blood pressure (BP) and heart rate (HR) were measured for 120 min, and for 24 h at 30 mg/kg. The IV injection of SR induced an immediate and dose-dependent decrease in BP. The maximal diastolic hypotension was situated between 11 p. 100 at 0.3 mg/kg and 45 p. 100 at 3 mg/kg (basal values: 133 +/- 6 and 131 +/- 5 mmHg). These effects lasted between 30 min and over 2 hours. The oral administration of SR induced a dose-dependent fall in BP at 3 mg/kg and upwards. The maximal diastolic hypotension appeared within 60 and 120 min and were situated between 8 p. 100 at 3 mg/kg and 28 p. 100 at 60 mg/kg (basal values: 130 +/- 7 and 133 +/- 2 mmHg). At 30 mg/kg, the hypotension lasted for 8 hours. SR was roughly 10 times less hypotensive in WKY than in SHR. HR did not change.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
3.
《Journal of Cardiothoracic Anesthesia》1988,2(3):346-355
Bepridil is an investigational calcium antagonist that also has fast sodium channel blocking and antidysrhythmic properties. In the present study, the potential interactions of bepridil with volatile anesthetics on cardiac electrophysiologic parameters were evaluated ] in open-chest dogs. Twenty-four dogs anesthetized with enflurane (n = 6), halothane (n = 6), isoflurane (n = 6), or chloralose (n = 6) received 2.5 mg/kg of bepridil intravenously (IV). Twenty-five additional dogs anesthetized with enflurane (n = 7), halothane (n = 6), isoflurane (n = 6), or chloralose (n = 6), received bepridil, 5.0 mg/kg, IV. Dogs anesthetized with cloralose served as controls. Cardiac electrophysiologic parameters were measured after the dogs were anesthetized and were repeated 5, 15, 30, 45, and 60 minutes after bepridil infusion. Plasma bepridil concentrations were also determined at the above time points. Synergy between bepridil and enflurane was demonstrated in the following cardiac electrophysiologic parameters: depression of sinus node function as evidenced by severe depression of sinus node automaticity and conduction; depression of atrioventricular function as evidenced by prolongation of the atrial—His bundle interval and the Wenckebach R-R interval; and, prolongation of the atrial effective refractory period. No synergy was demonstrated between bepridil and halothane or isoflurane when compared to bepridil's effects during chloralose anesthesia. It is concluded that significant synergistic cardiac electrophysiologic effects exist between bepridil and enflurane in dogs. It is recommended that caution be used when anesthetizing patients receiving bepridil with enflurane until human data on the use of this combination of pharmacologic agents is available. 相似文献
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5.
Effects of angiotensin converting enzyme inhibitor and calcium antagonist on endothelial function in patients with essential hypertension. 总被引:5,自引:0,他引:5
Young-Keun On Cheol-Ho Kim Byung-Hee Oh Myoung-Mook Lee Young-Bae Park 《Hypertension research》2002,25(3):365-371
The endothelium plays an important role in maintaining vascular tone and function. Essential hypertension is associated with alterations in endothelial function. The effects of antihypertensive agents on endothelial function have not been fully evaluated in human hypertension and data on the forearm circulation of humans are controversial. The aim of this study was to determine whether treatment with an angiotensin converting enzyme (ACE) inhibitor or a calcium antagonist improves endothelial dysfunction in hypertensive patients and whether the mechanism involved could be related to antioxidant activity. Endothelial function was estimated using venous occlusion plethysmography in 18 hypertensive patients and 11 healthy volunteers. The patients in the hypertension group were treated with enalapril or amlodipine. The change of forearm blood flow (FBF) was measured during acetylcholine infusion through the brachial artery and also during intra-arterial vitamin C infusion to explore the effects of vitamin C on responses to acetylcholine. FBF response to acetylcholine was significantly enhanced by intra-arterial infusion of vitamin C in the hypertensive group before antihypertensive treatment. Co-infusion of L-NMMA(N(G)-monomethyl-L-arginine), an inhibitor of nitric oxide synthase, blunted forearm blood flow response to acetylcholine. After antihypertensive treatment with enalapril or amlodipine for 2 months in the hypertensive group, endothelium-dependent vasorelaxation (vasodilatory response to acetylcholine) was significantly improved. Even though the mechanisms leading to depressed endothelial function in essential hypertension remain to be elucidated, our study shows that treatment with an ACE inhibitor or a calcium antagonist resulted in demonstrable improvement by a mechanism that is probably related to antioxidant activity. 相似文献
6.
Taddei S Virdis A Ghiadoni L Magagna A Favilla S Pompella A Salvetti A 《Hypertension》2001,37(3):943-948
Essential hypertension is associated with impaired endothelium-dependent vasodilation caused by oxygen free radical-induced nitric oxide (NO) breakdown. Because calcium antagonists can improve endothelial function in patients with essential hypertension, in this study we tested the hypothesis that this beneficial effect could be related to restoration of NO availability by antioxidant properties. In 15 healthy subjects and 15 hypertensive patients, we studied forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (ACh; 0.15, 0.45, 1.5, 4.5, and 15 microg/100 mL per minute), an endothelium-dependent vasodilator in basal conditions, during infusion of N:(G)-monomethyl-L-arginine (L-NMMA, 100 microg/100 mL forearm tissue per minute), an NO-synthase inhibitor, vitamin C (8 mg/100 mL forearm tissue per minute), and finally, simultaneous infusion of L-NMMA and vitamin C. The response to sodium nitroprusside (SNP; 1, 2, and 4 microg/100 mL forearm tissue per minute) was also evaluated. In control subjects, vasodilation to ACh was inhibited by L-NMMA and not changed by vitamin C. In hypertensive patients, vasodilation to ACh was blunted as compared with control subjects and resistant to L-NMMA. Vitamin C, which decreased plasma isoprostanes and increased plasma antioxidant capacity, increased the response to ACh and restored the inhibiting effect of L-NMMA. In hypertensive patients, the study was repeated after 3-month treatment with nifedipine gastrointestinal therapeutic system (30 to 60 mg/daily). Nifedipine treatment decreased circulating plasma lipoperoxides and isoprostanes and increased plasma antioxidant capacity. Moreover, nifedipine increased the vasodilation to ACh but not to SNP and restored the inhibiting effect of L-NMMA on ACh-induced vasodilation, whereas vitamin C no longer exerted its facilitating activity. These results indicate that nifedipine increases endothelium-dependent vasodilation by restoring NO availability, an effect probably determined by antioxidant activity. 相似文献
7.
Twelve patients with angiographically proven coronary artery disease and stable, exercise-induced angina pectoris were treated in a randomized sequence with placebo (PL) and bepridil tablets in maintenance doses of 200 mg, 400 mg and 600 mg per day for one week each, according to a double blind-protocol with intra-individual cross-over. The four treatment phases were separated by 2-week wash-out periods (placebo). On day 7 of each treatment phase and at the end of each wash-out period heart rate and blood pressure were measured 2 and 5 hours after drug intake and exercise stress testing was performed. The mean plasma concentrations at the end of the 1-week treatment periods 2 hours after drug intake were: 375 +/- 202 ng/ml (200 mg/day), 844 +/- 273 ng/ml (400 ng/day) and 1378 +/- 538 ng/ml (600 mg/day). Systolic blood pressure was not influenced by either bepridil dose. Diastolic blood pressure was slightly reduced (-6%) after 600 mg bepridil/day (p less than 0.05). While heart rate at rest in the upright position tended to lower values with regard to bepridil dosages, it was significantly lowered at the end of stress testing (2 hours/5 hours):400 mg: -7% (p less than 0.05)/-15% (p less than 0.05); 600 mg: -11% (p less than 0.001)/-10% (p less than 0.05). Myocardial ischemia (sum of ST-segment depressions) was improved in a dose-dependent manner (2 hours/5 hours):200 mg: -21% (p less than 0.05)/-31% (n.s.); 400 mg: -27% (n.s.)/-31% (p less than 0.01); 600 mg: -56% (p les than 0.001)/-55% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
8.
Tiapamil, a new calcium antagonist: hemodynamic effects in patients with acute myocardial infarction
The afterload reduction and myocardial oxygen sparing that results after administration of calcium antagonists suggests a possible role for these drugs in intervention after onset of acute myocardial infarction, but their use in this setting is limited by the possibility that left ventricular failure will develop. Tiapamil is a new verapamil congener. The hemodynamic effects of this drug (1 mg/kg followed by 25 micrograms/kg/min over 36 hr) were studied in 30 patients randomly assigned in a double-blind manner to a tiapamil or control group within 12 hr of the onset of acute myocardial infarction as diagnosed by Swan-Ganz catheterization and gated blood pool scans. Tiapamil reduced heart rate from 83 +/- 20 beats/min (mean +/- SD) before to 74 +/- 19 beats/min after drug (over an average 36 hr), arterial pressure from 128 +/- 22/87 +/- 14 to 118 +/- 16/74 +/- 11 mm Hg, rate-pressure product from 10,695 +/- 3492 to 8800 +/- 2550 units, and systemic vascular resistance from 1732 +/- 351 to 1400 +/- 350 dynes X sec X cm-5. Tiapamil also increased stroke volume index from 34.7 +/- 12.1 to 41.6 +/- 12.0 ml/m2, left ventricular ejection fraction from 50.1 +/- 14.8% to 56.4 +/- 17.4% (at 24 hr), left ventricular end-diastolic volume index from 71.3 +/- 23.1 to 80.5 +/- 23.7 ml/m2, and peak diastolic filling rate (an index of diastolic relaxation) from 2.1 +/- 0.9 to 2.6 +/- 0.8 end-diastolic volumes/sec (p less than .05 for all changes). Cardiac index, wedge pressure, left ventricular end-systolic volume, and PR interval remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
9.
Calcium antagonists effective in lowering blood pressure are a heterogeneous group including three main classes: phenylalkylamines, benzothiazepines and dihydropyridines. Dihydropyridines have a dual mode of action upon the endothelium contributing to their beneficial antihypertensive effects: (1) direct relaxation by inhibition of smooth muscle L-type calcium current, and (2) indirect relaxation through release of nitric oxide from the vascular endothelium. Calcium antagonists may affect many calcium-dependent events in the formation of atherosclerosis such as the localized accumulation of collagen, elastin, and calcium together with monocyte infiltration and smooth muscle proliferation and migration. In the INSIGHT calcification study, the overall treatment effect of nifedipine demonstrated significant inhibition of coronary calcium progression over a three-year period. Calcium antagonists improve symptoms and reduce ischemia in hypertensive patients with ischemic heart disease. Although in placebo-controlled trials calcium antagonists demonstrated a significant reduction in cardiovascular morbidity and mortality, they may be less effective than other types of antihypertensive drugs in preventing ischemic heart disease. 相似文献
10.
J. Wilson P. J. Commerford R. Scott Millar L. H. Opie 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》1992,6(1):41-46
Summary The aim of the study was to investigate the hemodynamic effects of a short-acting, potent, highly specific calcium antagonist,
nisoldipine, in patients with acute myocardial infarction. Twenty-four patients were selected on the basis of an elevated
wedge pressure and/or elevated blood pressure, less than 12 hours after the onset of symptoms. Patients were randomized to
receive either placebo or lowdose nisoldipine (2 μg/kg) as a single intravenous injection over a 3-minute period. Hemodynamic
effects were monitored for 20 minutes, and thereafter patients were crossed over to the other agent after the preserved parameters
had returned to baseline. An open-label study using double the dose of nisoldipine in 20 patients who had not reacted adversely
to low-dose nisoldipine followed. Standard hemodynamic monitoring showed that peak effects of nisoldipine were reached at
5 minutes, with some residual effect at 20 minutes, and it took up to 60 minutes to return to baseline. Both doses of nisoldipine
had similar effects: a fall in the systemic vascular resistance by about 600 units, variable tachycardia, little or no change
in the wedge pressure, a decrease in the arterial pressure, an unchanged rate-pressure product, and an increase in ejection
fraction. Tachycardia of more than 15 beats/min resulted in 5 of 24 patients with low-dose nisoldipine and 6 of 20 patients
with high-dose nisoldipine. In view of the risk of tachycardia, nisoldipine seems unsuitable for use in the acute phase of
myocardial infarction. 相似文献
11.
R Latini G Pierandrei L Achilli V Lombi F D'Amico 《Giornale italiano di cardiologia》1987,17(2):144-148
To evaluate the hypotensive efficacy of Verapamil alone and combined with diuretic, in the treatment of essential hypertension in elderly patients, we studied 54 patients, mean age 67.2 +/- 4.7 years, with essential hypertension, I-II WHO class. After a two-week wash-out from previous hypotensive therapies, patients were divided, at random, into three groups and, in double-blind conditions; they were treated as follows: the first group was treated with Verapamil (V) slow-release 240 mg/die, the second group with Chlorthalidone (C) 50 mg/die and the third group with the combination of Verapamil slow-release 240 mg/die and Chlorthalidone 50 mg/die (V + C). In the first group, the therapy (V) statistically reduced (p less than 0.001) either PAS or PAD values in supine position, (respectively -13 +/- 9 mmHg and -12 +/- 4 mmHg) and PAS-PAD values in upright position (respectively -16 +/- 3 mmHg and -10 +/- 3 mmHg). In the group treated with C, a statistically significant reduction (p less than 0.001) of PAS (-12 +/- 3 mmHg in supine position and -16 +/- 3 mmHg in upright position) and of PAD (-11 +/- 5 in supine and -9 +/- 4 mmHg in upright position). In the third group, V + C treatment induced a statistically bigger reduction of PAS and PAD (p less than 0.001) than that of the other two groups either in supine (-24 +/- 3 and -21 +/- 5 mmHg, respectively) or in upright position (-26 +/- 4 and -20 +/- 5 mmHg, respectively). Three patients interrupted the therapy for scarse compliance (I-II group).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
12.
张晓英 《中华老年心脑血管病杂志》2005,7(4):224-226
由各种肾脏疾病引起的高血压统称肾性高血压,包括肾实质性高血压、肾血管性高血压(如肾动脉粥样硬化性狭窄)及肾脏内分泌性高血压(如肾素瘤所致),其中肾实质性高血压最常见,占各种原因所致高血压的5%~10%,在继发性高血压中占第一位. 相似文献
13.
We studied the renal effects of nicardipine, a calcium entry blocker, in seven patients with mild-to-moderate essential hypertension. Glomerular filtration rate (GFR) and renal blood flow (RBF) were measured by means of thiosulfate and para-aminohippurate, respectively. Intravenous administration of nicardipine hydrochloride (0.5 mg) increased RBF by 26.8 +/- 5.8% (mean +/- SEM, p less than 0.01), GFR by 35.4 +/- 12.4% (p less than 0.05), and urinary excretion of sodium by 56.4 +/- 10.7% (p less than 0.05) with a significant (p less than 0.01) reduction in systolic and diastolic blood pressure as compared to control values. Nicardipine decreased total renal vascular resistance by 30.0 +/- 3.2% (p less than 0.05) from the control value, while filtration fraction remained unchanged. Our results indicate that nicardipine has several favorable renal effects with a concomitant hypotensive action in patients with mild-to-moderate essential hypertension. 相似文献
14.
刘玉梅 《心血管康复医学杂志》2009,18(2):102-104
目的:观察康复(非药物)治疗在高血压病(EH)治疗中的疗效。方法:门诊80例轻、中度EH患者被随机分为依那普利组(对照组)和康复组(各40例),康复组在依那普利治疗基础上增加康复治疗,对两组治疗4周、8周时的治疗有效率及血压数据进行统计学分析。结果:治疗4周时两组血压差异无显著性(P〉0.05),8周时总有效率康复组的显著好于对照组(82.5%:72.5%),血压也较对照组显著改善[(120.54±8.16):(127.14±10.71)mmHg/(80.10±9.25):(88.10±7.96)mmHg],差异有显著性(P均〈0.01)。结论:康复治疗在高血压治疗过程中疗效肯定,临床不可忽视。 相似文献
15.
I Kobrin C Amodeo H O Ventura F H Messerli E D Frohlich 《The American journal of cardiology》1985,55(6):722-725
Systemic, renal and splanchnic hemodynamics and certain reflex and endocrine responses were determined in 10 patients with essential hypertension before and after intravenous administration of urapidil, a new antihypertensive agent that acts through both central and peripheral alpha-adrenergic inhibitory mechanisms. The reduction in mean arterial pressure by 12% (103 +/- 3 vs 91 +/- 6 mm Hg, p less than 0.05) was mediated through a decreased total peripheral resistance index (from 34 +/- 2 to 25 +/- 3 U/m2, p less than 0.01), which was associated with a significant reflexive increase in cardiac index, heart rate and serum norepinephrine level. This hypotensive effect was also associated with blunted Valsalva overshoot and orthostatic hypotension, suggesting peripheral arteriolar and venular dilation. Renal and splanchnic blood flows increased (p less than 0.05), resistances in these vascular beds decreased (p less than 0.01) and there were no changes in creatinine clearance or glomerular filtration fraction. Thus, intravenous urapidil reduced arterial pressure by decreasing total peripheral, renal and splanchnic resistances associated with maintained organ flows and increased heart rate and cardiac index. 相似文献
16.
Horita Y Yakabe K Tadokoro M Suyama N Hayashida K Kawano Y Miyazaki M Kohno S Taura K 《American journal of hypertension》2006,19(3):282-285
BACKGROUND: Reports indicate that acetazolamide (ACZ) induces the vasodilation of all vessels in animal models, as well as in small and medium kidney vessels in animal models. However, the effect of ACZ on the renal circulation of patients with essential hypertension remains unknown. In this study we examined the effects of a carbonic anhydrase inhibitor, acetazolamide (ACZ), on the renal circulation of patients with essential hypertension. METHODS: We directly infused 1000 mg of ACZ into the main renal arteries of 10 patients with essential hypertension who had undergone cardiac catheterization. We then evaluated the effects of ACZ upon heart rate, renal artery blood pressure (BP), renal artery cross-sectional area, renal Doppler blood flow velocity, renal blood flow (RBF), and renal vascular resistance (RVR). RESULTS: The infusion of ACZ was not associated with any significant changes in heart rate or in systolic or diastolic BP. However, the velocity-time integral was increased by 11.1% +/- 7.2%, from 17.6 +/- 1.8 to 20.0 +/- 3.7 cm (P = .009); RBF was increased by 39% +/- 21%, from 300 +/- 43 to 422 +/- 96 mL/min/m(2) (P = .002); and RVR was reduced by 38% +/- 20% from 24,351 +/- 2,291 to 17,651 +/- 2,731 dynes.sec.cm(-5) (P < .01). In contrast the cross-sectional area of the renal artery did not change. CONCLUSIONS: The results of the present study demonstrated that ACZ has a potent vasodilatory effect on the renal circulation of patients with essential hypertension, leading to an obvious decrease in RVR and an increase in RBF. 相似文献
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The short-term (three months) effects of rilmenidine on systemic hypertension induced left ventricular hypertrophy (LVH) and left ventricular systolic and diastolic functions in comparison with those of perindopril and nifedipine-slow release (SR) formulation were studied. The short-term effects of rilmenidine on biochemical parameters and lipid profiles were evaluated. Sixty patients (39 men, 21 women) with a mean age of 59 +/- 14 years and with mild to moderate systemic arterial hypertension were enrolled in three groups. The first group received 1 mg/day of rilmenidine, the second group 4 mg/day of perindopril, and the third group 20 mg/day of nifedipine SR. All drugs induced a similar decrease in systolic and diastolic blood pressure (BP) values. Left ventricular mass (LVM) and LVM index decreased equally in all groups associated with a significant increase in the E/A ratio. The ratio between the reduction in LVM and decrease in mean arterial pressure (LVM/mmHg) was higher in groups 1 and 2. Negative correlations between LVM and LVMI. E/A, and the dv/dt ratio were obtained. Rilmenidine did not change the blood chemistry and lipid profile values. Despite its neutral effect on lipid profile and biochemical parameters. rilmenidine is as effective as perindopril and nifedipine in controlling hypertension and decreasing left ventricular hypertrophy. 相似文献
20.
Cytosolic calcium and insulin resistance in elderly patients with essential hypertension. 总被引:5,自引:0,他引:5
R L Byyny M LoVerde S Lloyd W Mitchell B Draznin 《American journal of hypertension》1992,5(7):459-464
We evaluated insulin sensitivity in normotensive (blood pressure, BP, less than 135/85 mm Hg) and hypertensive (BP greater than 160/90 mm Hg) elderly subjects over 65 years old who were stratified as normal weight (body mass index, BMI, less than 27) and obese (BMI greater than 27). Obese hypertensive individuals demonstrated marked hyperinsulinemia (P less than .01) and significantly reduced (P less than .05) submaximally stimulated adipocyte 2-deoxyglucose (2-DOG) uptake (abdominal wall fat biopsy). Normal weight hypertensive subjects also demonstrated higher levels of insulinemia and lower insulin-stimulated 2-DOG uptake than nonobese controls. Adipocyte [Ca2+]i levels were elevated in all elderly subjects compared to young individuals (P less than .01). Basal and maximally stimulated 2-DOG uptake were similar in all groups. One month of therapy with a calcium channel blocker, 10 mg nitrendipine twice daily, reduced blood pressure in the hypertensive subjects, reduced plasma insulin to control values during an oral glucose tolerance test in obese hypertensive individuals (P less than .01), and restored adipocyte 2-DOG uptake at submaximally effective insulin concentration to control values in normal weight and obese hypertensive subjects. In summary, older hypertensive, and particularly older obese hypertensive, patients manifest significant insulin resistance accompanied by elevated levels of [Ca2+]i in their adipocytes. 相似文献