Effect of nifedipine on splanchnic and pulmonary vascular capacitance

Summary. This study examines the hypothesis that nifedipine may increase splanchnic vascular capacitance and thus change the distribution of blood between the splanchnic and pulmonary circulation in heart failure patients. Relative regional blood volumes were determined by equilibrium blood pool scintigraphy during a 10 min baseline period and for 30 min after nifedipine 20 mg sublingually, with simultaneous recordings of systemic and pulmonary arterial pressures, hepatic venous wedge pressure, and cardiac output. Eight patients with ischaemic heart failure received nifedipine. Four patients served as controls. Nifedipine reduced mean arterial pressure and systemic vascular resistance in every patient. There were no significant changes in the relative blood volumes of the intestinal, hepatic, or splenic regions or in hepatic venous wedge pressure (reflecting portal venous pressure), suggesting unchanged splanchnic vascular pressure-volume relationship. Nifedipine caused a 6.3±l.0% increase in relative pulmonary blood volume and a slight increase in pulmonary vascular distending pressure from 16.1±2.9 mmHg to 17.5±2.8 mmHg (P < 0.05), suggesting that the increase in pulmonary blood volume was passively mediated. In conclusion, nifedipine did not change splanchnic vascular capacitance, but caused a small increase in pulmonary blood volume, which probably was a passive response to increased distending pressure.     

Forearm vascular responses in normotensives and hypertensives after sublingual nifedipine

Some hemodynamic variables of ten untreated hypertensives and nine normotensives were compared before and at 10, 30, and 60 min after nifedipine 10 mg sublingually. Serum nifedipine concentration was measured at each of these times, and was similar between groups. Resting forearm venous compliance did not differ between groups, and did not change after nifedipine. Nifedipine did not change mean arterial pressure significantly, but heart rate was increased in both groups. Resting forearm blood flow was significantly higher in hypertensives than normotensives and forearm vascular resistance was correspondingly lower. Forearm blood flow increased and vascular resistance fell after nifedipine in normotensives, but did not change significantly in hypertensives. Our data do not suggest any effect of nifedipine on peripheral venous compliance. We do not confirm the reported decrease in forearm venous compliance in hypertensives, but the characteristics of blood flow, vascular resistance, and lack of effect of nifedipine on blood pressure likely reflect a predominance of early hypertensives in our study population.     

The effects of oral nifedipine on hepatic blood flow in humans

Duplex ultrasonography was used to measure changes in hepatic blood flow in 13 healthy volunteers after they received single doses of 10 mg oral nifedipine and placebo. Blood flow was measured in the hepatic artery and branches of the portal and hepatic veins at baseline and 0.3, 0.6, 1, 1.5, 2, 3, 4, and 5 hours after drug administration. Cardiac output was also measured at baseline and 1, 2, and 3 hours after dosing. Blood flow initially increased in all three vessels 0.6 hour after administration of nifedipine (29%, 56%, and 31% in the hepatic artery, hepatic vein, and portal vein, respectively) compared with placebo. Flow rapidly returned to baseline in the hepatic artery and hepatic vein, whereas it appeared to remain elevated through 3 hours in the portal vein. Nifedipine administration resulted in an increase in cardiac output of 26%, 22%, and 14% above placebo at 1, 2, and 3 hours, respectively. No significant differences were detected in the systolic, diastolic, or mean arterial blood pressures after nifedipine or placebo. This study demonstrates that nifedipine increases hepatic blood flow in a transient nature and systemic hemodynamic parameters do not necessarily reflect specific organ responses. The nifedipine-induced change in blood flow should be considered when nifedipine is coadministered with high-clearance drugs, because systemic availability may be increased.     

Nifedipine kinetics and dynamics during rectal infusion to steady state with an osmotic system

Nifedipine steady-state kinetics and dynamics were investigated in a placebo-controlled study of six healthy subjects. Nifedipine was given rectally through an osmotic system at a zero-order rate for 24 hr. Steady-state plasma concentrations of approximately 20 ng/ml were achieved within 6 to 8 hr. Nifedipine lowered diastolic blood pressure (DBP) and increased forearm blood flow (FBF) and plasma norepinephrine concentration. On the other hand, heart rate (HR) and systolic blood pressure were not affected. Changes in DBP and FBF were closely related to nifedipine plasma concentrations during and immediately after the infusion period. Our data indicate that nifedipine lowers blood pressure in subjects with normotension and that it is possible by infusing the drug at a relatively low rate to dissociate its effect on blood pressure from that on HR.     

A comparison of the effects of two modified release preparations of nifedipine-nifedipine retard 10 mg twice daily and nifedipine GITS 20 mg once daily--in the treatment of mild to moderate hypertension

A multicentre, randomised, double-blind, cross-over comparison of nifedipine GITS 20 mg once daily and nifedipine retard 10 mg twice daily in 49 patients with mild to moderate hypertension was conducted. Both treatments resulted in clinically significant trough blood pressure reductions (nifedipine GITS -10.1/-8.9 mmHg, nifedipine retard -7.5/-8.2 mmHg). The study demonstrated that nifedipine GITS was 'at least equivalent' to nifedipine retard in the reduction of trough diastolic blood pressure (one-sided lower 95% confidence limit, -1.2 mmHg). The overall incidence of adverse events (nifedipine GITS 25.5%, nifedipine retard 34.0%), as well as the incidences of headache (nifedipine GITS 8.5%, nifedipine retard 12.8%) and peripheral oedema (nifedipine GITS 2.1%, nifedipine retard 8.5%), was higher with nifedipine retard compared to nifedipine GITS. Nifedipine GITS 20 mg once daily is 'at least equivalent' to nifedipine retard 10 mg twice daily in patients with mild to moderate hypertension, as well as being better tolerated.     

Renal effects of acute calcium blockade with nifedipine in hypertensive patients receiving beta-adrenoceptor-blocking drugs

The effects on blood pressure and renal function of a single 20-mg sublingual dose of nifedipine were investigated in 10 patients with mild to moderate arterial hypertension insufficiently treated on beta-blocker monotherapy. Nifedipine induced a prompt and marked reduction of both systolic and diastolic blood pressure (average maximal reduction 30/22 mm Hg, P less than 0.001). Despite the beta blockade, heart rate rose 25%. Only insignificant increments of glomerular filtration (RVR) was markedly reduced (P less than 0.001). Urinary excretion rate of albumin and beta-2 microglobulin rose after nifedipine, reflecting changes in glomerular as well as tubular function. Mean blood pressure seemed to be a major determinant of the excretion of proteins. There was a marked increase in the excretion of sodium after nifedipine and urine volume rose from a mean of 8.2 +/- 1.3 to 12.5 +/- 1.8 ml/min (P less than 0.01). The changes in sodium excretion rate correlated with the renal hemodynamic changes. Uric acid excretion rate rose remarkably after nifedipine and the magnitude of the changes seemed intimately related to the basal level of RVR. The results indicate that nifedipine therapy may be advantageous in patients whose hypertension is insufficiently controlled with beta blockers alone. Renal blood flow is maintained and there is a desirable diuretic action and enhancement of uric acid excretion.     

Comparative clinico-pharmacological characteristics of nimodipine,nifedipine and foridon in the treatment of patients with ischemic stroke in late rehabilitative and residual periods

A comparative study of pharmacodynamics and clinical efficacy of nimodipine, nifedipine and foridon in ischemic stroke (late recovery and residual period) was performed in 97 patients with ischemic stroke. It was found that nimodipine, nifedipine and foridon at late recovery or residual stages significantly improved higher psychic functions, promoted regression of neurologic disorders and optimized social rehabilitation. Nimodipine, primarily, decreased the intensity of neurological disorders, improved higher psychic functions and had a positive impact on cerebral hemodynamics. Nifedipine primarily improved central hemodynamics (increased stroke output and ejection fraction). Foridon is most effective selective pharmacodynamic impact on peripheral hemodynamics (stimulated arteriolar blood flow, diminished venous capacity and spasticity), i.e. normalized peripheral blood flow.     

硝苯地平联合卡托普利治疗原发性高血压的疗效研究

目的研究硝苯地平联合卡托普利治疗原发性高血压的疗效。方法收集本院收治的原发性高血压患者临床资料,在给予硝苯地平联合卡托普利治疗后,监测患者的血压、蛋白尿以及高血压引起的心绞痛缓解情况。结果用药后,2组平均血压值均发生明显下降,治疗组疗效明显好于对照组。对照组心绞痛的缓解情况明显好于治疗组,而治疗组治疗后24 h尿蛋白明显下降,低于对照组。结论硝苯地平和卡托普利对于原发性高血压有较好疗效,总体有效率达到95%,尤其对于伴有蛋白尿的高血压患者能够显著改善蛋白尿的状况。     

Treatment of hypertensive emergency

Objective To present the efficacy and tolerability of a new oral dosage form of the calcium antagonist nitrendipine compared to nifedipine capsules in patients with hypertensive emergency.Design Multicenter randomized double blind clinical study.Setting 23 study centres (hospitals) in Germany.Patients 161 patients between 20 and 70 years with acutely elevated blood pressure (systolic 200–250 mmHg, diastolic between 110–140 mmHg) with and without concomitant clinical symptoms.Interventions Double blind treatment with 10 mg nifedipine or 5 mg nitrendipine. Nifedipine was administered as capsules, nitrendipine was given from a small plastic tube (vial), containing 1 ml alcoholic solution. Every patient received in addition to the test medication a placebo corresponding to the other product. Patients with insufficient treatment after 45 min were given either an additional capsule of 10 mg nifedipine or a further vial containing 5 mg nitrendipine according to their group and maintaining the double dummy procedure.Measurements and results Blood pressure and heart rate were measured repeatedly during 4 h, before and 90 min after beginning of the treatment a 12 channel resting ECG was recorded. At 45 min after administration the blood pressure had fallen significantly from 216.0/117.4 mmHg to 170.0/93.3 mmHg under nifedipine and from 216.9/117.3 mmHg to 177.4/94.4 mmHg under nitrendipine. 61.6% of the nifedipine patients and 58.8% of the nitrendipine patients had already reached blood pressure values <180/100 mmHg after 45 min and in both groups 83% of these patients were still in this limit at the end of the observation period after 4 h. Tolerability was very good in both groups.Conclusion The new dosage form of nitrendipine (vial with 1 ml of alcoholic solution) represents an alternative in the treatment of hypertensive emergency.     

Arginine8-vasopressin reduces spinal cord blood flow after spinal subarachnoid injection in rats

Arginine8-vasopressin (AVP) causes hindlimb paralysis, loss of nociceptive responsiveness and increased arterial pressure after spinal subarachnoid injection in rats. In these experiments, the effects of paralytic intrathecal doses of AVP on rat brain and spinal cord blood flow, vascular resistance and cardiac output were measured using radiolabeled microspheres. Ten minutes after injection, AVP (10-100 pmol) elevated mean arterial pressures significantly, increased vascular resistances in thoracic and lumbosacral spinal cord and reduced blood flow to the lumbosacral spinal cord without altering cardiac output, total peripheral resistance and blood flow to brain and other spinal cord regions. Lumbosacral blood flows remained significantly reduced 30 min after injection of 100 pmol of AVP, and recovered to pretreatment base-line levels by 60 min postinjection. Lactic acid concentrations were elevated significantly in spinal cerebrospinal fluid samples removed 5 to 15 min after AVP injection (100 pmol). The selective AVP V1 receptor antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(O-methyl)tyrosine] arg8-vasopressin, which previously blocked the effects of AVP on hindlimb motor and nociceptive function, in these experiments also blocked the AVP-induced increases in arterial pressure and reductions in lumbosacral perfusion. Intravenous infusion of the vasodilators papaverine and nifedipine failed to block AVP-induced hindlimb paralysis. Nifedipine, however, did accelerate subsequent recovery of hindlimb motor function, although it did not alter the lumbosacral blood flow reductions measured at 10 and 30 min after AVP injection. These findings indicate that AVP has significant vascular effects in the rat spinal cord that are associated with ischemia and neurological dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nifedipine gastrointestinal therapeutic system--hypertension management to improve cardiovascular outcomes

Hypertension is a major cardiovascular risk factor, and its increasing prevalence is of great clinical concern. Despite the availability of numerous effective therapies, hypertension remains under-diagnosed and under-treated. Hypertension often coexists with other risk factors, and current guidelines recommend a multifactorial approach to management, with the aim of not only controlling blood pressure but also reducing overall cardiovascular risk. Nifedipine gastrointestinal therapeutic system (GITS) is a long-acting formulation of a calcium channel blocker. Once-daily dosing with nifedipine GITS has been shown to achieve smooth and continuous blood pressure control, identical to conventional first-line diuretic therapy. Small-scale clinical trials have also shown that nifedipine GITS positively affects markers of atherosclerotic disease, which may signify an additional clinical benefit, but this is yet to be demonstrated. The recently completed ACTION (A Coronary Disease Trial Investigating Outcome with Nifedipine GITS) trial provides further evidence that nifedipine GITS can be used safely in high-risk patients to treat angina, lower blood pressure and significantly improve clinical outcomes.     

Rate of increase in the plasma concentration of nifedipine as a major determinant of its hemodynamic effects in humans

The relevance of the rate of increase in the plasma concentration of nifedipine for the drug's hemodynamic effect was investigated in healthy volunteers. Nifedipine was given intravenously according to two regimens, each designed to produce the same steady-state concentration, but attained gradually (within 5 to 7 hours) with one regimen and rapidly (within 3 minutes) with the other. The mean steady-state concentrations obtained were 31.7 +/- 5.2 (SD) ng/ml and 29.4 +/- 9.8 ng/ml, respectively (not significant). With the gradual regimen, heart rate was unchanged and diastolic blood pressure was lowered gradually by approximately 10 mm Hg. With the rapid regimen, heart rate increased immediately and remained elevated for the duration of the infusion, whereas diastolic blood pressure did not change significantly. At the end of the gradual-rise regimen, the infusion rate was increased tenfold for 10 minutes, promptly resulting in tachycardia and a paradoxical rise in diastolic blood pressure. These divergent hemodynamic responses of the gradual- and rapid-rise regimens could well be related to differences in baroreceptor activation. It is concluded that the hemodynamic response to nifedipine is influenced by the rate of increase of its concentration in plasma.     

Efficacy and Safety of Nifedipine Coat-Core versus Amlodipine in Patients With Mild to Moderate Essential Hypertension: Comparison of 24-Hour Mean Ambulatory Diastolic Blood Pressure

BACKGROUND: Calcium channel blockers have been successfully used for the treatment of hypertension. In this study, the antihypertensive efficacy and safety of the dihydropyridine calcium channel blockers nifedipine coat-core 30 mg and amlodipine 5 mg were evaluated. METHODS: This multicenter, double-blind, prospective, randomized, parallel-arm study compared once daily administration of nifedipine coat-core 30 mg with once daily amlodipine 5 mg in subjects with mild-to-moderate essential hypertension. A 4-week placebo run-in period was followed by an 8-week active treatment period. Blood pressure reduction was measured by ambulatory blood pressure monitoring and casual office blood pressure measured by mercury sphygmomanometer. RESULTS: Nifedipine coat-core and amlodipine produced equivalent reductions in mean diastolic blood pressure, as determined by 24-hour ambulatory blood pressure monitoring. Mean reduction in diastolic blood pressure was 5.4 mmHg and 5.8 mmHg for nifedipine coat-core and amlodipine, respectively. Both drugs were well tolerated and neither treatment resulted in a significant change in heart rate. CONCLUSIONS: Nifedipine coat-core 30 mg once-daily is comparable to amlodipine 5 mg once-daily for blood pressure reduction.     

Nifedipine and telmisartan for the treatment of hypertension: the TALENT study

A combination of two drugs as initial treatment in patients with a high or very high cardiovascular risk profile is recommended. Nifedipine extended release (GITS) is a calcium-channel antagonist known to be metabolically neutral, to mildly slow the development of atherosclerosis in hypertensive subjects and to significantly decrease cardiovascular risk in diabetic patients. Telmisartan is highly selective for the angiotensin receptor 1, it gives a greater improvement in glycemic and lipid control compared with irbesartan, and it proved its superiority in improving insulin sensitivity compared with eprosartan. The TALENT study was aimed to determine whether combining low-dose nifedipine GITS at and telmisartan reduced ambulatory and clinic blood pressure more than the two components in monotherapy in hypertensive patients at high cardiovascular risk. The study shows that combination treatment with nifedipine GITS and telmisartan provides a greater and earlier blood pressure reduction than the combination components in monotherapy.     

Effects of nicorandil, a new antianginal agent, and nifedipine on collateral blood flow in a chronic coronary occlusion model

The effects of nicorandil and nifedipine on collateral blood flow were compared in anesthetized dogs with a well-developed collateral circulation produced by Ameroid constriction (6-8 weeks) of the left anterior descending (LAD) coronary artery. The radioactive microsphere technique was used to determine myocardial perfusion in the normal left circumflex (LC) region and in the LAD region distal to the Ameroid constrictor. Low and high doses of nicorandil (25 and 50 micrograms/kg/min) or nifedipine (1 and 3 micrograms/kg/min) were infused i.v. to reduce mean arterial and left ventricular systolic pressure approximately 10 and 25 mm Hg, respectively. A low dose of nicorandil had no effect on myocardial perfusion whereas nifedipine increased subepicardial blood flow in both the LC and LAD regions. The high dose of nifedipine further increased both subepicardial and subendocardial perfusion to the LC region and subepicardial blood flow to the LAD region whereas nicorandil had no effect. When aortic blood pressure was returned to control by occluding a snare around the descending thoracic aorta during infusion of the high dose, nicorandil and nifedipine increased subepicardial and subendocardial blood flow to LAD and LC regions. Whereas nicorandil increased flow to both tissue layers equally, nifedipine increased subepicardial perfusion primarily. In summary, nifedipine increased collateral blood flow in a chronic coronary occlusion model despite the presence of systemic hypotension, whereas nicorandil only increased flow when aortic blood pressure was maintained. However, nicorandil increased myocardial blood flow equally across the left ventricular wall, whereas nifedipine primarily increased subepicardial blood flow.     

Nifedipine and telmisartan for the treatment of hypertension: the TALENT study

A combination of two drugs as initial treatment in patients with a high or very high cardiovascular risk profile is recommended. Nifedipine extended release (GITS) is a calcium-channel antagonist known to be metabolically neutral, to mildly slow the development of atherosclerosis in hypertensive subjects and to significantly decrease cardiovascular risk in diabetic patients. Telmisartan is highly selective for the angiotensin receptor 1, it gives a greater improvement in glycemic and lipid control compared with irbesartan, and it proved its superiority in improving insulin sensitivity compared with eprosartan. The TALENT study was aimed to determine whether combining low-dose nifedipine GITS at and telmisartan reduced ambulatory and clinic blood pressure more than the two components in monotherapy in hypertensive patients at high cardiovascular risk. The study shows that combination treatment with nifedipine GITS and telmisartan provides a greater and earlier blood pressure reduction than the combination components in monotherapy.     

硝苯吡啶控释片对脑卒中伴高血压患者运动功能的影响

目的探讨硝苯吡啶控释片对脑卒中伴高血压患者血压控制及肢体运动功能的作用。方法对80例脑卒中伴高血压患者给予运动治疗、作业治疗及神经营养。随机分为治疗组60例和常规组20例。治疗组每天加服硝苯吡啶控释片30mg。治疗过程中2组每日2次测血压,在治疗前及治疗4周后分别采用简式Fugl-Meyer及Barthel指数评定肢体运动功能及日常生活能力(ADL)。结果治疗组降压显效率高于常规组,且血压波动小;治疗组ADL评定增高较常规组显著(P＜0.05);治疗组肢体运动功能改善,以下肢明显(P＜0.05)。结论硝苯吡啶控释片降压效果平稳可靠,并能促进脑卒中患者运动功能的恢复。     

Effect of efonidipine, a novel dihydropyridine derivative, on myocardial metabolic changes induced by coronary artery ligation in dogs: comparison with nifedipine

Summary— Efonidipine is a dihydropyridine derivative having a vasodilating action, which is slower in onset and longer in duration than that of nifedipine. In the present study, we compared the effects of efonidipine with those of nifedipine on the ischemic myocardial metabolism in anesthetized dogs. The heart was made ischemic by ligating the left anterior descending coronary artery (LAD) completely for 3 or 30 min. Efonidipine or nifedipine was injected intravenously, 10 or 3 min, respectively, before the start of LAD occlusion. Efonidipine (0.01 or 0.03 mg/kg) decreased both blood pressure and heart rate, whereas nifedipine (0.003 mg/kg) decreased blood pressure and increased heart rate. The magnitude of decrease in mean blood pressure induced by 0.03 mg/kg efonidipine was similar to that induced by 0.003 mg/kg nifedipine. Although efonidipine did not modify the changes in myocardial carbohydrate metabolism induced by ischemia, it attenuated the ischemia-induced decrease in the myocardial level of adenosine triphosphate and energy charge potential. Nifedipine, however, did not modify the changes in both myocardial energy and carbohydrate metabolism induced by ischemia. The results suggest that efonidipine has a cardioprotective effect in the dog, probably because of its negative chronotropic effect.     

Combination of nifedipine and carteolol compared to nifedipine alone in diurnal blood pressure variation and exercise blood pressure in patients with essential hypertension.

A combination of nifedipine (40 mg twice daily) plus carteolol (10 mg twice daily) was compared with nifedipine monotherapy in ten patients with essential hypertension. Ambulatory blood pressure (BP) monitoring over 24 hours and treadmill exercise testing were performed before treatment with nifedipine (but after the placebo period), after four weeks of nifedipine treatment, and after four weeks of nifedipine+carteolol combination therapy. At the end of nifedipine monotherapy, 24-hour average ambulatory BP, minimum ambulatory BP during sleep, maximum ambulatory BP, and casual BP all decreased significantly (P less than 0.01). However, the standard deviation (SD) of the ambulatory BP was not affected. The change in systolic BP response to treadmill exercise increased. After a four-week period of nifedipine+carteolol combination therapy, average ambulatory BP and maximum ambulatory BP were further decreased (P less than 0.01). The SD of the ambulatory BP and the change in BP response to exercise were significantly decreased (P less than 0.01), but the minimum ambulatory BP was not affected. These findings suggest that nifedipine and carteolol differ in their influence on diurnal BP variation and on exercise-induced BP elevation. Carteolol may mainly attenuate stress-induced BP elevation and have little influence on nocturnal BP decline. In contrast, nifedipine may affect the BP profile uniformly over the entire day. Nifedipine+carteolol combination therapy may be superior to nifedipine monotherapy because carteolol has a minimal effect on nocturnal BP and decreases stress-induced BP elevation.     

Acute efficacy of a sublingual dose of nifedipine on uterine arterial blood flow: preliminary data in prematurely menopausal women.

OBJECTIVES: To determine whether the calcium blocker nifedipine alters Doppler velocimetry and impedance parameters in the uterine artery in prematurely menopausal women. METHODS: Uterine artery Doppler examinations were performed transvaginally in seventeen prematurely menopausal women without the use of calcium blocker (T0). Following a 10-mg sublingual dose of nifedipine patients were subsequently rescanned at successive time intervals (T25 = 25, T40 = 40, T60 = 60 min). PI (normalized (NPI) for heart rate) and maximum, minimum and average velocities of the uterine artery were recorded and waveforms were qualitatively assessed using Goswamy and Steptoe's waveform classification. RESULTS: Quantitative analysis showed a significant decrease in NPI at T(25) in the right and left uterine arteries (T0: PI = 2.95 and 3.01; T25: PI = 1.52 and 1.52, respectively; P < 0.001) and until the end of the experiment. Minimum and average blood flow velocities increased strongly (P < 0.001) whereas the maximum velocities did not change significantly (P = 0.12). Qualitative analysis revealed more conspicuous results: eight subjects presented 'abnormal' spectra: one was type A (absence of protodiastole), three were type B (absence of telediastole) and four were type O (no diastolic blood flow); all of them recovered type C waveforms (normal spectrum) during the hour following nifedipine administration. CONCLUSIONS: Nifedipine induces a reversible decrease in NPI and an increase in blood flow velocities in the uterine artery in prematurely menopausal women. These results suggest that nifedipine is a potent uterine arterial vasodilator.