Doses Of Nifedipine Research Articles

24‐hour blood pressure monitoring to evaluate the effects of nifedipine in pre‐eclampsia and in chronic hypertension in pregnancy

To investigate the effect of 7 to 14 days of therapy with nifedipine (sustained-release preparation) on the 24-hour blood pressure patterns of pregnant women with pre-eclampsia or chronic hypertension, and to test the utility of blood pressure monitoring in modulating the timing and dosage of the drug. 24-hour automatic blood pressure monitoring of pregnant women with pre-eclampsia or chronic hypertension before and after nifedipine treatment. Centre for Prevention, Diagnosis and Treatment of Hypertension in Pregnancy, University of Turin, Italy. Sixteen pregnant women with pre-eclampsia and 17 with chronic hypertension. 24-hour blood pressure monitoring was performed before the beginning of the therapy and after 7 to 14 days of treatment with sustained-release nifedipine. Chronobiological analysis of systolic and diastolic blood pressure values was performed; MESOR, amplitude, acrophase, hyperbaric index, percent time elevation and significance of rhythm were calculated before and after treatment. 6336 blood pressure measurements were analysed. Systolic and diastolic MESOR values were significantly decreased after nifedipine treatment both in pre-eclampsia and in chronic hypertension. However, the antihypertensive effect of nifedipine in pre-eclampsia was especially pronounced during evening and night, while in chronic hypertension it was more constant during the 24-hour period. 24-hour blood pressure monitoring allowed adjustment, when necessary, to the timing and dosage of nifedipine in accordance with the blood pressure patterns of each patient, using the hyperbaric index and percent time elevation as objective parameters for the evaluation of treatment efficacy. 24-hour blood pressure monitoring is a good method to optimise treatment, and confirms that nifedipine is useful for the control of maternal blood pressure in pregnancy.

Calcium channel subtypes in porcine adrenal chromaffin cells.

The effects of nifedipine, omega-conotoxin GVIA (omega-CgTx) and omega-agatoxin IVA (omega-AgTx) on Ca2+ currents, a 60-mM-K+-induced increase in intracellular Ca2+ concentration (-Ca2+-i) and catecholamine secretion were examined to clarify the subtypes of Ca2+ channels in cultured adrenal chromaffin cells from the pig. Nifedipine, omega-CgTx, and omega-AgTx inhibited Ca2+ currents in a dose-dependent manner, suggesting the presence of L-, N- and P-type Ca2+ channels. The maximal doses of nifedipine (10 microM), omega-CgTx (1 microM), and omega-AgTx (0.1 microM) inhibited Ca2+ currents to 85%, 22%, and 94% of control currents, respectively. The inhibitory effects of these three blockers were observed in the same cell, indicating that at least three subtypes of Ca2+ channels are present in porcine chromaffin cells. The increase in -Ca2+-i and catecholamine secretion induced by 60 mM K+ were inhibited equally by nifedipine (10 microM) and omega-CgTx (1 microM), but not by omega-AgTx (0.1 microM). These results suggest that L-, N- and P-type Ca2+ channels are present in porcine adrenal chromaffin cells, and that the major pathways of Ca2+ entry evoked by a high concentration of K+ are L- and N-type Ca2+ channels.

Characterization of Voltage-Sensitive Calcium Channels in Growth Plate Chondrocytes

Growth plate chondrocytes (GPCs), cells integrally involved with the process of endochondral bone formation, facilitate Ca2+ infux to provide a source of ion for processes such as Ca2+ signaling and matrix vesicle loading. We hypothesize that this Ca2+ entry into GPCs is achieved through the action of voltage-sensitive Ca2+ channels. This hypothesis was tested by measuring intracellular [Ca2+] changes in fura 2-loaded GPCs that were depolarized by challenge with a K(+)-containing medium. KCl doses between 55 and 95 mM evoked significant Ca2+ responses that were blocked by addition of extracellular EGTA. The Ca2+ response evoked by 95 mM K+ was insensitive to 100 microM doses of nifedipine or nitrendipine, ruling out L-type channel involvement. This finding was corroborated by the observation that 10 microM BAY K 8644 did not activate a Ca2+ response of its own. However, 10 microM Cd2+ significantly inhibited the 95 mM Ks(+)-evoked effects, suggesting N-type channel activity. Use of 1 microM Ni+ in an attempt to block possible T-type channel activity caused nonspecific cellular effects, precluding pharmacological assessment of a possible T-type channel activity. These data (i) provide the first direct evidence for voltage-sensitive Ca2+ channel activity in GPCs and (ii) suggest at least partial facilitation of that activity through N type channels.

D20 Efficacy of a low dose nifedipine gits (20 mg) in patients with mild to moderate hypertension

D20 Efficacy of a low dose nifedipine gits (20 mg) in patients with mild to moderate hypertension

Meta-analysis of the Long-term Effect of Nifedipine for Pulmonary Hypertension

Pulmonary hypertensive disorders generally result in a progressively worsening course associated with substantial morbidity and mortality. Nifedipine therapy may provide an effective solution to attenuate the disease state. To assess the magnitude and consistency of the effect of nifedipine on reducing pulmonary artery pressure in patients with pulmonary hypertensive disorders. A meta-analysis of 8 trials of nifedipine therapy. Clinical trials were identified by a computerized literature search of MEDLINE and by an assessment of bibliographies of retrieved studies. Trials were selected if they measured the change in pulmonary artery pressures in their subjects after weeks to months of therapy. Eight of 25 conducted trials were selected for review. Meta-analysis of 6 homogeneous trials demonstrated a significant decrease in pulmonary artery pressure: -7 mm Hg (95% confidence interval, -3 to -11 mm Hg; P < .01). Heterogeneity of trial results appeared to be due to differences in the severity of initial pulmonary artery pressures and to differences in the dosage of nifedipine rather than the type of disease state. Meta-analysis of the trials of nifedipine therapy in patients with pulmonary hypertension demonstrated a decrease in pulmonary artery pressure that was associated with an amelioration of clinical symptoms. Because of the paucity of data, however, larger trials are needed to better define its clinical value.

Nifedipine for Hypertensive Emergencies

To the Editor. —Dr Grossman and colleagues1mention the practical problems associated with the administration of sublingual nifedipine. As an alternative method to cutting the capsule and squeezing its contents into the patient's mouth, nurses and physicians may frequently attempt to withdraw the liquid contents of the capsule using a needle and syringe. We investigated the accuracy and precision of this method of administration. The preparation of 10-mg doses of nifedipine was simulated by requesting 20 pharmacy staff to withdraw the total contents of a liquid-filled nifedipine capsule (Adalat, 10 mg, Bayer, Auckland, New Zealand) by puncturing the gelatin shell and withdrawing the contents into a preweighed 1-mL needle and syringe. The 10-mg capsules contain 0.34 mL of liquid nifedipine, which has a density of 1.135 gm/L (written communication, data on file, Bayer, Auckland, New Zealand). After removal of the dose, each syringe and needle was reweighed, and the amount of nifedipine

Nifedipine pharmacological variables as risk factors for gingival overgrowth in organ-transplant patients.

The prevalence and severity of gingival overgrowth in organ-transplant patients medicated with cyclosporin are greater in patients concomitantly medicated with nifedipine; however, no relationship between the gingival overgrowth and any of the nifedipine pharmacological variables has been demonstrated. The study examined the effect of five nifedipine pharmacological variables (nifedipine dosage, plasma concentration and gingival crevicular fluid concentration, M1 metabolite plasma concentration and the nifedipine: M1 ratio). The effect of the nifedipine variables on the gingival overgrowth score were examined using univariate and multivariate regression analysis. Adjustment for the effect of other risk factors was made by adding the distribution of each of the nifedipine variables in turn to a stepwise regression model containing previously identified risk factors for this condition. Despite the high levels of nifedipine sequestered in the GCF, only the plasma concentration of nifedipine was identified as a risk factor for the severity of gingival overgrowth in these patients (P = 0.01) once adjusted for other known risk factors (R2 for the model = 55%).

Modulation of Calcium Channels in Human Erythroblasts by Erythropoietin

Erythropoietin (Epo) induces a dose-dependent increase in intracellular free Ca2+ ([Ca2+]i ) in human erythroblasts, which is dependent on extracellular Ca2+ and blocked by high doses of nifedipine or Ni2+. In addition, pretreatment of human erythroblasts with mouse antihuman erythropoietin receptor antibody but not mouse immunopure IgG blocked the Epo-induced [Ca2+]i increase, indicating the specificity of the Ca2+ response to Epo stimulation. In this study, the erythropoietin-regulated calcium channel was identified by single channel recordings. Use of conventional whole cell patch-clamp failed to detect Epo-induced whole cell Ca2+ current. To minimize washout of cytosolic constituents, we next used nystatin perforated patch, but did not find any Epo-induced whole cell Ca2+ current. Using Ba2+ (30 mmol/L) as charge carrier in cell-attached patches, we detected single channels with unitary conductance of 3.2 pS, reversal potential of +72 mV, and whose unitary current (at +10 mV) increased monotonically with increasing Ba2+ concentrations. Channel open probability did not appreciably change over the voltage range (−50 to +30 mV) tested. Epo (2 U/mL) increased both mean open time (from 4.27 ± 0.75 to 11.15 ± 1.80 ms) and open probability (from 0.26 ± 0.06 to 2.56 ± 0.59%) of this Ba2+-permeable channel. Our data strongly support the conclusion that the Epo-induced [Ca2+]i increase in human erythroblasts is mediated via Ca2+ entry through a voltage-independent Ca2+ channel.

Modulation of Calcium Channels in Human Erythroblasts by Erythropoietin

AbstractErythropoietin (Epo) induces a dose-dependent increase in intracellular free Ca2+ ([Ca2+]i ) in human erythroblasts, which is dependent on extracellular Ca2+ and blocked by high doses of nifedipine or Ni2+. In addition, pretreatment of human erythroblasts with mouse antihuman erythropoietin receptor antibody but not mouse immunopure IgG blocked the Epo-induced [Ca2+]i increase, indicating the specificity of the Ca2+ response to Epo stimulation. In this study, the erythropoietin-regulated calcium channel was identified by single channel recordings. Use of conventional whole cell patch-clamp failed to detect Epo-induced whole cell Ca2+ current. To minimize washout of cytosolic constituents, we next used nystatin perforated patch, but did not find any Epo-induced whole cell Ca2+ current. Using Ba2+ (30 mmol/L) as charge carrier in cell-attached patches, we detected single channels with unitary conductance of 3.2 pS, reversal potential of +72 mV, and whose unitary current (at +10 mV) increased monotonically with increasing Ba2+ concentrations. Channel open probability did not appreciably change over the voltage range (−50 to +30 mV) tested. Epo (2 U/mL) increased both mean open time (from 4.27 ± 0.75 to 11.15 ± 1.80 ms) and open probability (from 0.26 ± 0.06 to 2.56 ± 0.59%) of this Ba2+-permeable channel. Our data strongly support the conclusion that the Epo-induced [Ca2+]i increase in human erythroblasts is mediated via Ca2+ entry through a voltage-independent Ca2+ channel.

Suppressive effects of Bay K 8644 on toxicity of calcium channel blockers in cultured rat embryos.

Previous study revealed that calcium channel blockers (CCBs) reduced embryonic heart rates (HRs) and produced morphological abnormalities when Gestational Day (GD) 11.5 rat embryos were cultured for 20 hr. The present study was to investigate whether a calcium channel agonist, Bay K 8644 (BAY), prevented CCB-induced embryotoxicity in vitro. GD 11.5 embryos were exposed to nifedipine (NIF), diltiazem (DIL), and verapamil (VER) either alone or in combination with BAY at 0.1, 1.0, and 10 micrograms/ml. These doses of BAY alone had no effect on gross morphology. Embryonic HRs were increased at 10 micrograms/ml of BAY, but were within control levels at 0.1 and 1.0 microgram/ml. The doses of NIF, DIL, and VER were 40, 6.0, and 2.0 micrograms/ml, respectively, and were the minimum concentrations to produce a 100% effect on morphological abnormalities. Embryonic HRs were reduced to 22, 31, and 34% below control levels in the NIF, DIL, and VER groups, respectively. The negative chronotropic effects of CCBs were inhibited by coadministration with BAY, depending on its concentration. When embryos exposed to each CCB were supplemented with BAY at 1.0 or 10 micrograms/ml, embryonic HRs were comparable to those of controls. Combined exposures of each CCB and 10 micrograms/ml BAY did not cause any morphological abnormalities. These results suggested that mechanisms of CCB embryotoxicity were directly related to pharmacological consequences of calcium channel blockage in developing rats.

“Inappropriate” physician habits in prescribing oral nifedipine capsules in hospitalized patients

Despite the absence of an approved Food and Drug Administration (FDA) indication, the use of oral or "sublingual" nifedipine for hypertension in the hospitalized patient has become an increasingly common practice. The purpose of the study was to assess the clinical circumstances for which the drug was being prescribed and the practices of attending and resident physicians. Dosing of oral nifedipine capsules in medical and surgical inpatients was studied prospectively in three central Connecticut hospitals (University, community-teaching, and private nonteaching) during a 60-day period from January to March, 1994. Through evaluation of computerized pharmacy and medical records, data were collected on diagnostic reasons for ordering nifedipine, pre- and posttreatment blood pressures, dosing frequency, clinical documentation associated with drug prescription, and adverse events. Physicians and nurses at the respective hospitals were unaware of the conduct of the study. The incidence of nifedipine capsule administration at all three hospitals was 3.4% (152 dosings in 83 patients/4489 hospitalized patients/ 60 days). Practice habits and blood pressure changes differed minimally among hospitals and physicians. Sixty-three percent of nifedipine orders were given over the telephone for arbitrary and asymptomatic blood pressure elevations and 98% of the orders lacked bedside patient evaluation. Follow-up of the blood pressure was performed within 1 h in 51% of patients and within 2 h in 24%, while in 25% there was no documentation of follow-up until 2 to 6 h after nifedipine dosing. Mean pretreatment blood pressure was 186/94 +/- 20/16 mm Hg (range: 150 to 260 mm Hg systolic and 50 to 125 mm Hg diastolic). Blood pressure fell 32/16 +/- 22/16 mm Hg (range: -92 to +8 mm Hg systolic and -90 to +28 mm Hg diastolic) and was related to the level of pretreatment blood pressure (r = 0.53 for systolic blood pressure, and r = 0.49 for diastolic blood pressure, P < .001 for both). Large, asymptomatic blood pressure reductions were common. One hypertensive patient experienced severe hypotension accompanied by an anterior wall myocardial infarction. These data demonstrate inappropriate physician prescribing of oral nifedipine in hospitalized patients characterized by a lack of proper assessment prior to drug dosing, highly arbitrary treatment parameters that were written without regard for symptoms or underlying illnesses, and slow follow-up for evaluation of the clinical response to therapy.

Porcine coronary artery pharmacodynamics in vitro evaluated by a new intravascular technique: Relation to axial stretch

A new intravascular balloon catheter-based technique, impedance planimetry and the wire-mounted isometric tension technique commonly employed to study vessel pharmacodynamics in vitro, were compared. Porcine left anterior descendent coronary artery reactivity to nifedipine was assessed and the influence of 20% axial stretch was investigated. There were no histological differences between segments where the impedance planimetry balloon had been inflated and untouched segments. EC 50 values differed significantly between the three procedures applied: The isometric method ( n = 7): 2.54 ± 0.44 · 10 −9 M; nonstretched arteries by the impedance planimetric method ( n = 7): 1.99 ± 0.40 · 10 −8 M; arteries 20% axially stretched ( n = 7): 2.00 ± 1.36 · 10 −7 M (isometric and nonstretched: p < 0.05; isometric and stretched: p < 0.001; nonstretched and stretched: p < 0.05). Maximal relaxant responses to nifedipine were 91.8 ± 2.1% (isometric method), 105.1 ± 2.3% (nonstretched), and 104.9 ± 7.7% (stretched) (ANOVA, p = 0.11). In stretched arteries, the initial 12-min response to an increased dose of nifedipine was more rapid than the response of nonstretched arteries at a concentration of 1 · 10 −7 M ( p = 0.038) and had a nonsignificant tendeney toward a more rapid response at other concentrations. Resting tone could not be demonstrated and time control experiments showed no change in the maximal vessel response to potassium with any of the three methods. A new method in the evaluation of artery pharmacodynamics in vitro was presented. The study demonstrated that axial stretching of an artery has impact on the pharmacodynamic reactivity to nifedipine in porcine coronary arteries. Further studies are needed to evaluated the impact of the method on endothelial function.

Hemodynamic effects of oral nifedipine in preeclamptic hypertensive emergencies

OBJECTIVE: Our purpose was to evaluate the hemodynamic effects of oral nifedipine in preeclamptic hypertensive emergencies. STUDY DESIGN: A prospective observational study of the hemodynamic effects of oral nifedipine was conducted with severely preeclamptic patients receiving magnesium sulfate infusion during a hypertensive emergency. Patients were eligible for the study if systolic blood pressure was ≥170 m Hg or the diastolic blood pressure was ≥105 mm Hg on repeat measurements 15 minutes apart at ≥24 weeks' gestation. Nifedipine was given with an initial dose of 10 mg orally followed by 20 mg orally every 20 minutes until systolic blood pressure was <160 mm Hg and the diastolic blood pressure was <100 mm Hg, or for a total of five doses. Patients were hemodynamically monitored in the lateral recumbent position by thoracic electrical bioimpedance before during, and after oral nifedipine dosing. Cardiac index, systemic vascular resistance index, mean arterial pressure, heart rate, and stroke index were all recorded at baseline and during treatment. Data were analyzed by analysis of variance for repeated measures (α 0.05) and by paired t tests, baseline versus 15 minutes ( α 0.01). RESULTS: Ten severely preeclamptic patients at 33.2 ± 3.0 (mean ± SD) weeks' gestation were enrolled in the study. Mean arterial pressure measurements taken at baseline, 0.25, 0.5, 1, and 4 hours were 133 ± 10, 119 ± 8, 109 ± 8 89 ± 12, and 100 ± 13 mm Hg (mean ± SD, p < 0.0001, analysis of variance repeated measures). Cardiac index increased over time ( p = 0.0011, analysis of variance repeated measures). There was no significant effect on maternal heart rate or stroke index. No periodic fetal heart rate changes were noted. One patient had nausea. CONCLUSION: Oral nifedipine appears to be an effective antihypertensive agent in preeclamptic hypertensive emergencies. A steady decrease in mean arterial pressure, systemic vascular resistance, and a mirrored increase in cardiac index are noted. (Am J Obstet Gynecol 1996;175:336-40.)

Digital pulse plethysmography as a non-invasive method for predicting drug-induced changes in left ventricular preload.

Changes in the contour of the plethysmographically recorded digital pulse curve after nitrate ingestion are well known, but it has not been fully established whether these changes reflect nitrate action on left ventricular (LV) preload or afterload. Therefore, we compared the pulse wave contour after administration of equieffective doses of nitroglycerin and nifedipine. In 20 patients with coronary artery disease we measured aortic blood pressure curve in the aorta ascendens, digital volume pulse curve with a photoelectric pulse pickup, Riva Rocci blood pressure and heart rate after administration of either 0.8 mg nitroglycerin or 10 mg nifedipine. Peak plasma concentrations of nitroglycerin and nifedipine were achieved 5 min and 20 min after ingestion of the drugs. Systolic aortic blood pressure decreased after both nitroglycerin and nifedipine to 19.4 mmHg, but diastolic blood pressure decreased only after nifedipine by 10.5 mmHg (P < 0.05). Riva Rocci blood pressures showed a similar time course. Heart rate increased from 67.4 to 70.9 beats.min-1 after nitroglycerin and from 58.9 to 69.4 beats.min-1 after nifedipine. The calculated a/b ratio of the aortic pressure curve increased after both medications (nitroglycerin, from 1.66 to 1.99; nifedipine, from 1.66 to 1.93) and its time course mimicked that of the systolic blood pressure. The a/b ratio of the digital pulse curve did not change after nifedipine, but showed a pronounced rise after nitroglycerin from 1.29 to 1.84. With regard to pharmacological actions, nitroglycerin causes a reduction in LV preload and afterload, whereas nifedipine has only LV-afterload-reducing activity. We conclude, that the reduction in afterload did not cause the typical changes in wave contour of the peripheral pulse curve which occur with organic nitrates. Most likely changes in the a/b ratio reflect changes in LV preload.

Lack of Effect of Orlistat on the Bioavailability of a Single Dose of Nifedipine Extended‐Release Tablets (Procardia XL) in Healthy Volunteers

Orlistat, a lipase inhibitor, reduces dietary fat absorption, and thus could potentially alter the absorption of some concomitantly administered drugs, such as the nifedipine gastrointestinal therapeutic system (GITS). To assess the effect of orlistat on the bioavailability of nifedipine GITS, a third party-blind, placebo-controlled, randomized, two-way crossover study was performed in 18 healthy volunteers. Each participant received single 60-mg oral doses of nifedipine GITS (Procardia XL; Pfizer Labs, New York, NY) on the fourth day of treatment with 120 mg of orlistat or placebo three times a day for 6 days. The two treatments were separated by a washout period of at least 1 week. Serial blood samples were collected before and at appropriate intervals after each nifedipine dose to determine plasma concentrations of nifedipine. The 90% confidence intervals for the ratio of geometric least-square means for maximum concentration (C(max)) and area under the concentration-time curve (AUCo-t) and for the difference of arithmetic least-square means for time to maximum concentration (t(max)) indicate that the bioavailability of nifedipine was not altered by treatment with orlistat. Therapeutic doses of 120 mg of orlistat three times daily do not significantly alter the bioavailability of a single 60-mg oral dose of nifedipine GITS in healthy volunteers.

The calcium channel blocker controversy.

A major controversy about the safety of calcium channel blockers (CCBs) has arisen since the publication of a case-control study showing that hypertensives who suffered an acute myocardial infarction (MI) were more likely than hypertensives who had not had an MI to be taking one of these (short-acting) agents than other antihypertensive agents. This study was accompanied by a republication of older studies showing that large doses of short-acting nifedipine given to post-MI patients increased their mortality rate. The danger of massive doses of short-acting nifedipine in a post-MI patient is real but irrelevant to current practice. On the other hand, the putative dangers of short-acting CCBs in the treatment of hypertension do not apply to the current use of long-acting CCBs. Therefore the scare over their use is both irrational and unfortunate.

Protective effect of nifedipine on myocardial stunning in isolated rabbit hearts: role of high energy phosphates stores.

The aim of the present study was to evaluate the effects of a single dose of nifedipine on myocardial stunning in isolated rabbit hearts. Hearts from rabbits pretreated with a single dose of 20 mg of nifedipine (NIF group) 1-4 h before isolation were compared to control hearts in their response to 15 min of global ischemia (37 degrees C) followed by 30 min of reperfusion. Both experimental groups showed similar baseline cardiac contractility. At the end of the reperfusion period in the control group, isovolumic left ventricular developed pressure (LVDP) and +dP/dtmax had stabilized at 45 +/- 2 and 48 +/- 2% of preischemic values respectively and in the NIF group LVDP stabilized at 63 +/- 6 and +dP/dtmax at 66 +/- 6% (P < 0.05 with respect to the control group). Left ventricular end diastolic pressure (LVEDP) values were significantly lower at the end of reperfusion in the NIF group compared to the controls (36.8 +/- 5.5 mmHg vs 53.4 +/- 3.9 mmHg, P < 0.05). The early impairment of the time constant of relaxation (tau) observed in control hearts was attenuated by pretreatment with nifedipine (control delta tau = 55 +/- 10 ms; NIF group delta tau = 29 +/- 5 ms, P < 0.05). Tissue ATP and creatine phosphate (CP) levels in the control group at the end of reperfusion were 6.9 +/- 0.7 and 8.7 +/- 0.7 mumol/g dry tissue, respectively; in the NIF group ATP and CP levels were significantly higher, 9.2 +/- 0.7 and 11.5 +/- 0.9 mumol/g dry tissue respectively (P < 0.05). Creatine kinase (CK) and lactate dehydrogenase (LDH) leakage during reperfusion were significantly higher in the control group (CK = 120 +/- 15 mU/ml and LDH = 60 +/- 8 mU/ml) compared to the NIF group (CK = 82 +/- 5 mU/ml and LDH = 41 +/- 2 mU/ml, P < 0.05). Our results demonstrate that pretreatment with a single oral dose (20 mg) of nifedipine attenuates systolic and diastolic functional alterations as well as the metabolic impairment associated with stunning in the isolated rabbit heart.

Drug-induced alteration of endothelial permeability in the rat aorta. Potential consequences on the vessel wall.

We recently reported that some diuretics affect capillary permeability in the normotensive rat. In the present study, we explore the effect of selected antihypertensive drugs administered orally during 10 days, on Evans blue (EB) extravasation within the wall of the thoracic (TA) and abdominal aorta (AA) obtained from spontaneously hypertensive rats (SHR). Description of the EB method has been previously reported. Daily doses (mg/kg) of captopril (CAP: 3.0), perindopril (PER: 0.3), nifedipine (NIF: 1.0), clentiazem (CLE: 0.1), hydralazine (HYD: 0.5), furosemide (FUR: 0.5), cicletanine (CIC: 2.0), hydrochlorothiazide (HCZ: 0.5), and indapamide (IND: 0.04) resulted in comparable blood pressure reduction. Percent changes in EB tissue concentration (measured in ug/g dry tissue) was increased by 24% in both the TA and AA in the untreated SHR. CAP reduced by half EB leakage in the TA, while PER decreased EB extravasation 16% below baseline values. Both angiotensin converting enzyme inhibitors failed to normalize EB leakage in the AA. The calcium channel blockers also normalized EB extravasation in the two segments of the aorta, except that CLE was without effect in the AA. HYD normalized EB leakage in the TA, but not in the AA. All diuretics tested reduced EB extravasation by 48 to 58% below baseline values in the TA, whereas CIC only normalized EB leakage. None of the diuretics affected EB extravasation in the AA of the SHR. 1-the two segments of the aorta were similarly affected in the SHR; 2-despite comparable effect on blood pressure, treatment of the SHR was associated with different responses in the TA and AA; 3-within a given class of drugs, different effects are observed on EB.

Gingival overgrowth in paediatric cardiac transplant patients: a study of 19 patients aged between 2 and 16 years.

It is well established that both cyclosporin and nifedipine are associated with gingival overgrowth. However, there is little information on the prevalence of this undesirable effect in paediatric patients. The present study investigated gingival overgrowth in 19 cardiac transplant patients aged 2 years 8 months to 16 years 3 months (1.5-8.5 years post-transplant) and related such changes to variables of daily cyclosporin dosage, trough blood cyclosporin concentration and daily nifedipine dosage. Ten patients showed clinically significant gingival overgrowth and nine relatively minor overgrowth; there was no significant difference between the two groups with respect to age, length of time post-transplant, cyclosporin dosage, whole blood concentration of cyclosporin or intake of nifedipine. The expression of gingival changes therefore did not relate to any drug variable in this group of subjects.

Long‐Term Survival and Use of Antihypertensive Medications in Older Persons

To determine whether older persons with hypertension who use specific calcium antagonists and ACE inhibitors have a different risk of mortality than those using beta-blockers. A prospective cohort study continuing from 1988 through 1992. Three communities of the Established Populations for Epidemiologic Studies of the Elderly. Hypertensive participants aged > or = 71 years (n = 906) who had no evidence of congestive heart failure and who were using either beta-blockers (n = 515), verapamil (n = 77), diltiazem (n = 92), nifedipine (n = 74), or ACE inhibitors (n = 148). Nifedipine was of the short acting variety. The main outcome measure was all-cause mortality. Age, gender, smoking, HDL-cholesterol, blood pressure, intake of digoxin and diuretics, physical disability, self-perceived health, and comorbid conditions were examined as confounders. During 3538 person-years of follow-up, 188 participants died (53 deaths per 1000 person-years). Compared with beta-blockers, after adjusting for age, gender, comorbid conditions and other health-related factors, the relative risks (95% confidence interval) for mortality associated with use of verapamil, diltiazem, nifedipine, and ACE inhibitors were 0.8 (0.4-1.4), 1.3 (0.8-2.1), 1.7 (1.1-2.7), and 0.9 (0.6-1.4), respectively. The results were unchanged after excluding participants with other potential contraindications to beta-blockers and after stratifying on coronary heart disease and use of diuretics. Higher doses of nifedipine were associated with higher mortality. Compared with beta-blockers, use of short acting nifedipine was associated with decreased survival in older hypertensive persons. However, selective factors influencing the use of specific drugs in higher risk patients could not be completely discounted, and final conclusions will depend on clinical trials.