Chronic Management of Hypertension after Stroke: The Role of Ambulatory Blood Pressure Monitoring / 대한뇌졸중학회지

Hypertension is the most important potentially reversible risk factor for stroke in all age groups; high blood pressure (BP) is also associated with increased risk of recurrent stroke in patients who have already had an ischemic or hemorrhagic event. Twenty-four hour ambulatory BP monitoring (ABPM) has become an important tool for improving the diagnosis and management of hypertension, and is increasingly used to assess patients with hypertension. Nevertheless, although ABPM devices are increasingly used for assessment of hypertension, their value in the chronic management of hypertension in patients with stroke has not been systematically studied. In fact, among large-scale randomized trials for secondary stroke prevention, only the Morbidity and Mortality After Stroke, Eprosartan Compared With Nitrendipine for Secondary Prevention trial included 24-hour ABPM. ABPM has demonstrated chronic disruption of the circadian rhythm of BP after acute phase of stroke and has shown higher sensitivity compared to office BP in evaluating the effectiveness of antihypertensive treatment among stroke survivors. High 24-hour BP is an independent predictor for cerebrovascular events, brain microbleeds, and subsequent development of dementia. Nevertheless, although stroke care guidelines endorse the importance of hypertension management, the specific role of ABPM among stroke survivors after the acute phase of disease has not been established. Further studies are needed to clarify whether routine application of ABPM among these patients should be recommended.

Chronic Management of Hypertension after Stroke: The Role of Ambulatory Blood Pressure Monitoring / 대한뇌졸중학회지

Hypertension is the most important potentially reversible risk factor for stroke in all age groups; high blood pressure (BP) is also associated with increased risk of recurrent stroke in patients who have already had an ischemic or hemorrhagic event. Twenty-four hour ambulatory BP monitoring (ABPM) has become an important tool for improving the diagnosis and management of hypertension, and is increasingly used to assess patients with hypertension. Nevertheless, although ABPM devices are increasingly used for assessment of hypertension, their value in the chronic management of hypertension in patients with stroke has not been systematically studied. In fact, among large-scale randomized trials for secondary stroke prevention, only the Morbidity and Mortality After Stroke, Eprosartan Compared With Nitrendipine for Secondary Prevention trial included 24-hour ABPM. ABPM has demonstrated chronic disruption of the circadian rhythm of BP after acute phase of stroke and has shown higher sensitivity compared to office BP in evaluating the effectiveness of antihypertensive treatment among stroke survivors. High 24-hour BP is an independent predictor for cerebrovascular events, brain microbleeds, and subsequent development of dementia. Nevertheless, although stroke care guidelines endorse the importance of hypertension management, the specific role of ABPM among stroke survivors after the acute phase of disease has not been established. Further studies are needed to clarify whether routine application of ABPM among these patients should be recommended.

The effect of niflumic acid and blocker of calcium channel on the desensitization of gamma aminobutyric acid-activated current / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the modulatory effect of niflumic acid and blocker of calcium channel on the desensitization of gamma aminobutyric acid (GABA)-activated currents in dorsal root ganglion(DRG) neurons from rat.</p><p><b>METHODS</b>The whole-cell patch-clamp technique was used to observe the modulatory effect of niflumic acid and blocker of calcium channel on the desensitization of GABA-activated currents in neurons freshly dissociated from rat DRG neurons.</p><p><b>RESULTS</b>Application of GABA (0.1-1 000 micromol/L) could induce concentration-dependent inward currents in some cells (212/223, 95.11%). GABA-(100 micromol/L) activated currents was (1.32 +/- 0.74) nA (n = 84). However, pre-application of niflumic acid (1-100 micromol/L) and nitrendipine (specific blocker of L-calcium channel)(0.1-30 micromol/L) could inhibit the GABA-activated inward current which was identified to be GABAA receptor-mediated current. The inhibitory effects of niflumic acid and nitrendipine were concentration-dependent. The suppression rate of 10 micromol/L niflumic acid and nitrendipine to GABA-activated currents were (31.60% +/- 4.87%) (n = 19) and (43.60% < or = 5.10%) (n = 5), respectively. The desensitization of GABA-activated currents had double exponential characteristic. Tau value was (14.68 +/- 5.11) s (n = 6) and (175.8 +/- 42.67) s (n = 6, r = 0.9647), respectively. Pre-application of niflumic acid (100 micromol/L) and nickel chloride (nonspecific blocker of L-calcium channel) (100 micromol/L) altered tau value of the desensitization of GABA-activated currents, tau value reduced for (4.64 +/- 2.21) s (n = 3), (43.70 +/- 14.34) s ( n = 3, r = 0.9548) and (4.64 +/- 2.21) s (n = 3), (43.70 +/- 14.34) s (n = 3, r = 0.9721).</p><p><b>CONCLUSION</b>Pre-application of niflumic acid exerts a more strong inhibitory effect on the peak value of GABA-activated current, which possibly is through blocking the calcium-activated chloride ion channel to accelerate the desensitization of GABA-activated currents.</p>

Analysis of therapeutic effects of rural patients with hypertension by combination administration of low dosage of hydrochlorothiazide and nitrendipine / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the therapeutic effects of combination administration of hydrochlorothiazide and nitrendipine at low dosage in the treatment of rural hypertension patients.</p><p><b>METHODS</b>By the method of cluster random sampling, 5292 primary hypertension patients from Fuxin, Liaoning Province were divided into health education group (control group) and drug intervention group in June 2006. The drug intervention group were treated with hydrochlorothiazide, nitrendipine and captopril by stepwise approach and we observe the antihypertensive effect of drug and the effect on the onset of stroke.</p><p><b>RESULTS</b>The average follow-up time was 15 months. At last, 308 patients were lost to follow-up (the lost follow-up rate was 5.8 percent). The 4984 in cohort, including 2530 of intervention group and 2454 of control group, had examination of all indicators. Through health education and drug intervention, the average blood pressure in drug intervention group decreased by 16.1/9.4 mm Hg (1 mm Hg = 0.133 kPa) while the average blood pressure in control group decreased by 6.7/3.5 mm Hg. The control rate of blood pressure in drug intervention group was higher than control group (33.1% vs. 15.1%, P < 0.001). Through drug intervention, the morbidity risk of nonfatal stroke in drug intervention group decreased by 57.3% compared to control group, the total morbidity risk of stroke decreased by 59.4%. The results had significant statistical difference. And, the morbidity of severe hypopotassaemia (K(+) < 3.0 mmol/L) and diabetes mellitus had no significant statistical difference between two groups.</p><p><b>CONCLUSIONS</b>The low-cost antihypertensive program based on thiazide had good antihypertensive effect, high safety and good cost-effect ratio. The program could be used in rural areas of China.</p>

Study on skin toxicology and penetration enhancement of skin absorption of volatile oil extracted from tender branchers of Camellia oleifera / 中国中药杂志

<p><b>OBJECTIVE</b>To study the toxicity on skin and penetration effect of volatile oil from tender branchers of Camellia oleifera on nitrendipine, baicalin, nimesulide for percutaneous obsorption.</p><p><b>METHOD</b>Acute skin toxicity, irritation and allergy on rats were tested, and mouse skin in vitro was applied for studying the effects of different concentrations of volatile oil in nitrendipine, baicalin, nimesulide on drug permeation.</p><p><b>RESULT</b>Different dosage volatile oil had no acute toxicity, irritation or hypersensitive effects. Compared to azone, more powerful enhancement effects of volatile oil at different concentration on nitrendipine, baicalin, nimesulide were very obvious.</p><p><b>CONCLUSION</b>This paper firstly reported the results of experiment about the toxicity to skin and penetr-ation effect of volatile oil from tender branches of C. oleifera.</p>

Acute and chronic effects of nitrendipine on naloxone precipitated morphine withdrawal in mice

There is growing evidence indicating that neuronal calcium channels play an important role in the mechanism of morphine dependence. In this study, the effects of acute and chronic administration of nitrendipine on naloxone precipitated morphine withdrawal signs were investigated. Mice were rendered dependent to morphine by subcutaneous injection of morphine over a period of 5 days. In chronic studies, nitrendipine [25 and 50 mg/kg, i.p.], or vehicle injections were given once a day during the morphine treatment, and the last injection of nitrendipine was given 24 h before the morphine withdrawal. For acute studies, nitrendipine [25 and 50 mg/kg, i.p.] was given 1 h after the last dose of morphine [1 h before naloxone]. A single injection of nitrendipine at 25 mg/kg was ineffective in blocking most signs of morphine withdrawal, however, at 50 mg/kg nitrendipine blocked signs such as hair raising, sniffing, diarrhea and number of jumping. The concurrent injections of nitrendipine with morphine prevented most signs of morphine withdrawal. In agreement with previous findings, these results suggest that alterations in voltage-sensitive calcium channels play a role in the adaptations that occur on chronic treatment with morphine

Evaluation of in vitro/in vivo correlation for three kinds of self-designed sustained-release nitrendipine formulations using deconvolution method / 药学学报

<p><b>AIM</b>To evaluate the in vitro/in vivo correlation for three kinds of self-designed sustained-release nitrendipine formulations using deconvolution method.</p><p><b>METHODS</b>The characteristics of in vivo release were calculated by deconvolution method using the data of plasma concentration of three kinds of self-designed sustained-release nitrendipine formulations in healthy dogs, in which the in vivo results of nitrendipine solution after oral administrated to dogs were used as weight function. It was the compared with characteristics of in vitro release to assess the in vitro/in vivo correlations.</p><p><b>RESULTS</b>The good correlations of in vitro/in vivo were shown in three kinds of self-designed sustained-release nitrendipine formulations using deconvolution method.</p><p><b>CONCLUSION</b>The deconvolution method exhibited advantage in evaluation of in vitro/in vivo correlation for self-designed sustained-release nitrendipine formulations.</p>

Preparation of sustained-release nitrendipine microspheres with a solid dispersed structure in liquid system / 药学学报

<p><b>AIM</b>To prepare the sustained-release nitrendipine microspheres with a solid dispersed structure in liquid system.</p><p><b>METHODS</b>The sustained-release nitrendipine microspheres with a solid dispersed structure was prepared in liquid system by combining spherical crystallization technique and solvent deposition method in one step. The resultant microspheres were evaluated for the recovery, micromeritc properties, incorporation efficiency. The factors of effect on the formation and the release rate of microspheres were also investigated.</p><p><b>RESULTS</b>The recovery of microspheres (280-900 microns) was more than 70% and the bulk density was around 0.7 kg.L-1. The incorporation efficiency always exceeded 95%. The formation of microspheres was mainly affected by the amount of bridging liquid and the emulsifying agents in poor solvent. The release rate of nitrendipine from the microspheres could be controlled as desired by adjusting the ratio of talc to Eudragit RS PO in the formulation.</p><p><b>CONCLUSION</b>The presented method was suitable for preparing sustained-release microspheres of a water insoluble drug.</p>

Papel de los calcio-antagonistas en el control de ventos vaso-oculsivos y hemolíticos en drepanocitosis: estudio piloto con nitrendipina / Paper of the calcium-antagonists in the control of events occlusives and hemoliticos in sickle cell disease: study pilot with nitrendipin

Recientemente se inició el estudio de fármacos capaces de inhibir la pérdida de agua y K+ del glóbulo rojo dependiente de Ca++, mediante el bloqueo del canal de gardos, como medida terapéutica para evitar el fenómeno de falciformación. Nuestro estudio intenta establecer el rol de la nitrendipina en el control de las manifestaciones clínicas y paraclínicas en drepanocitosis. Se realizó un estudio clínico controlado con placebo, randomizado, bajo protocolo simple ciego, de grupo en paralelo, con dos niveles de dosis, de 10 semanas de duración. Se incluyeron 26 pacientes (16 mujeres y 10 hombres) aleatoreamente distribuidos en tres grupos para recibir placebo o nitrendipina a 20 mg/día o nitrendipina a 30 mg/día. En ambos grupos de tratamiento con nitrendipina se apreció una tendencia hacia una menor frecuencia de eventos vaso-oclusivos con una menor proporción de pacientes afectados, pero sin lograr una diferencia estadísticamente significativa en las medias de evento por paciente, ni de intensidad medida en cada grupo. La nitrendipina logró una reducción significativa en el porcentaje de reticulocitos y en los niveles de bilirrubina indirecta basales en ambos niveles de dosis con respecto al placebo (comparación intergrupo e intragrupo: p<0.005). El resto de los parámentros no se modificaron. La droga fue bien tolerada. La nitrendipina redujo algunos marcadores de hemólisis (porcentaje de reticulocitos y BI). El verdadero potencial terapéutico de este agente debe ser confirmado en nuevos protocolos clínicos controlados

Unchanged protein level of ryanodine receptor but reduced (3H) ryanodine binding of cardiac sarcoplasmic reticulum from diabetic cardiomyopathy rats

The ryanodine receptor, a Ca2+ release channel of the sarcoplasmic reticulum (SR), is responsible for the rapid release of Ca2+ that activates cardiac muscle contraction. In the excitation-contraction coupling cascade, activation of SR Ca2+ release channel is initiated by the activity of sarcolemmal Ca2+ channels, the dihydropyridine receptors. Previous study showed that the relaxation defect of diabetic heart was due to the changes of the expressional levels of SR Ca2+ ATPase and phospholamban. In the diabetic heart contractile abnormalities were also observed, and one of the mechanisms for these changes could include alterations in the expression and/or activity levels of various Ca2+ regulatory proteins involving cardiac contraction. In the present study, underlying mechanisms for the functional derangement of the diabetic cardiomyopathy were investigated with respect to ryanodine receptor, and dihydropyridine receptor at the transcriptional and translational levels. Quantitative changes of ryanodine receptors and the dihydropyridine receptors, and the functional consequences of those changes in diabetic heart were investigated. The levels of protein and mRNA of the ryanodine receptor in diabetic rats were comparable to these of the control. However, the binding capacity of ryanodine was significantly decreased in diabetic rat hearts. Furthermore, the reduction in the binding capacity of ryanodine receptor was completely restored by insulin. This result suggests that there were no transcriptional and translational changes but functional changes, such as conformational changes of the Ca2+ release channel, which might be regulated by insulin. The protein level of the dihydropyridine receptor and the binding capacity of nitrendipine in the sarcolemmal membranes of diabetic rats were not different as compared to these of the control. In conclusion, in diabetic hearts, Ca2+ release processes are impaired, which are likely to lead to functional derangement of contraction of heart. This dysregulation of intracellular Ca2+ concentration could explain for clinical findings of diabetic cardiomyopathy and provide the scientific basis for more effective treatments of diabetic patients. In view of these results, insulin may be involved in the control of intracellular Ca2+ in the cardiomyocyte via unknown mechanism, which needs further study.

Anticonvulsant profile of nimodipine and nitrendipine against pentylenetetrazole induced seizures in rats.

The activity of nimodipine and nitrendipine against pentylenetetrazole (PTZ) induced seizures in Albino rats was studied alone and in combination with valproate. The median effective dose [ED50] of valproate, nimodipine and nitrendipine were initially determined. All the 3 drugs were injected i.p. 30 min before the induction of seizures. Seizures were induced by PTZ 85 mg/kg i.p., and subsequently the effect of combining ED50 doses of nimodipine and nitrendipine with ED50 dose of valproate was evaluated. ED50 of valproate and nitrendipine were 129 and 2.5 mg/kg respectively. ED50 of nimodipine could not be established since a dose-response relationship was not obtained. Hence, for the purpose of combination studies, 4 mg/kg of nimodipine was used. Both nimodipine (4 mg/kg) and nitrendipine (2.5 mg/kg) decreased the ED50 of valproate from 129 to 40 mg/kg. Both nimodipine and nitrendipine potentiate the activity of valproate against PTZ induced seizures and can be considered as potential adjuvant anticonvulsants which merit further study.

Eficacia de la nitrendipina en pacientes obesos hipertensos / Nitrendipine in obese hipertensive patients

La obesidad puede producir resistencia a la terapia antihipertensiva. La nitrendipina es un bloqueador de los canales del calcio de la familia de las dihidropiridinas, es efectivo en el manejo de la hipertensión arterial y ha demostrado mejorar la sensibilidad a la insulina. Para evaluar la eficacia de la nitrendipina en el control de la presión arterial del paciente hipertenso obeso, 20 pacientes adultos no diabéticos, obesos hipertenso obeso, 20 pacientes adultos no diabéticos, obesos hipertensos que no controlaron su presión arterial con modificaciones al estilo de vida pero sin manejo farmacológico, recibieron tratamiento farmacológico con 10 mg de nitrendipina una vez al día durante cuatro semanas. En todos los pacientes se realizó una prueba de tolerancia a la glucosa antes y después del estudio. Todos los pacientes redujeron la presión arterial a las dos semanas, persistiendo el control hasta el final del estudio. (p< 0.0001). La nitrendipina también mejoró significativamente la tolerancia a la glucosa de esos pacientes, especialmente a los 30 (p< 0.0008), 60 (p< 0.009) y 90 (p< 0.09) minutos, aunque no se observó cambio significativo a los 120 minutos (p> 0.2). Estos resultados sugieren que la nitrendipina tiene eficacia terapéutica como monoterapia en sujetos hipertensos obesos, no diabéticos con resistencia a la insulina

Study on the 3HAcetylcholine Release Induced by Oxygen-Glucose Deprivation in Rat Cerebral Cortical Slices

BACKGROUND: It has been shown that cerebral ischemia alters brain acetylcholine (Ach) metabolism. In an attempt to elucidate the mechanisms for ischemia-induced release of Ach in vitro, the effects of drugs which can influence the cholinergic neurotransmission on the ischemia-induced release of [3H]Ach from cerebral cortical slices of the rat were examined. METHODS: The cortices of decapitated rats were chopped and dispersed in artificial CSF. Then, the tissue suspensions were incubated with [3H]choline. The tissues were transferred and incubated in washing, hypoglycemic (deprivation of glucose), ischemic (deprivation of oxygen and glucose) and extracting plates sequently. Ischemia-induced release of [3H]Ach was expressed as percentage of the total [3H]Ach present in the slices. RESULTS: Ischemia induced significant release (about 9.3% of total tissue content) of [3H]Ach from cerebral cortical slices in vitro. This [3H]Ach release was significantly attenuated by tetrodotoxin, a voltage-sensitive Na+-channel blocker, and Mg2+, a physiological N-methyl-D-aspartate (NMDA) receptor blocker. Vesamicol (1 M), a blocker of vesicular transport of Ach, MK-801 and ketamine, NMDA receptor antagonists, 6,7-nitroquinoxaline-2,3-dione (DNQX) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), kainate/AMPA receptor antagonists, and 6-nitro-7-sulphamoylbenzo[f]quinoxaline-2,3-dione (NBQX), a AMPA receptor blocker attenuated the [3H]Ach. Nitrendipine, nimodipine, inhibitor of L-type Ca2+ channels, and -conotoxin GVIA, an inhibitor of N-type Ca2+ channels, significantly attenuated the ischemia-induced release of [3H]Ach. Omission of Ca2+ from incubation media attenuated the ischemia-induced [3H]Ach release. Inhibitors of intracellular Ca2+ release, dantrolene and TMB-8, and a cell-permeable calcium chelator, 1,2-bis (2-aminophenoxy)-ethane-N, N, N+, N+-tetraacetic acid tetrakis (acetoxymethyl) ester (BAPTA-AM), inhibited the ischemia-evoked [3H]Ach release. CONCLUSION: These results suggest that the ischemia can induce Ach rele.

Hipertensión renovascular y soplo abdominal en un caso: ¿ha modificado la tecnología su interpretación? / Renovascular hipertension and abdominal bruit: diagnostic implications of modern technological assessments: report of one case

A lateral abdominal bruit is considered an important finding for the detection of renovascular hypertension. However, the precision and accuracy of new techniques such as angiography, Doppler ultrasound and studies with radioisotopes have changed its value and clinical interpretation. We report a 75 years old woman with a bilateral renal artery stenosis in whom a bruit was heard over the artery that did not contribute to the genesis of hypertension and the significant arterial stenosis causing hypertension was silent. This particular situation could lead to erroneous clinical decisions

Conversión de sandimmune a neoral en pacientes trasplantados renales que reciben ciclosporina-ketoconazol / Conversion of sandimmune to neoral in patients with renal transplantation treated with cyclosporine-ketoconazol

Patients and methods: Thirty four patients with more than one year after the transplantation, with stable renal function and receiving triple immunosuppression were studied. Conventional cyclosporine was changed to the microemulsion form maintaining the same daily dose. Drug serum levels, serum creatinine and blood pressure were measured within two to eight months after the conversion. Doses of microemulsion cyclosporine were adjusted to achieve serum levels of 150 ñ 40 ng/ml. Results: Microemulsion cyclosporine induced a slight initial increase in blood cyclosporine levels. Afterwards, levels were more stable than with conventional cyclosporine (165-185 and 145-210 ng/ml respectively) and the dispersion of values were lower (standard deviations of 70 and 100 ng/ml respectively). Twenty three patients did not require dose adjustments, in four it was reduced and in five it was increased. There were no changes in serum creatinine or blood pressure after the conversion. Conslusion: More stable serum levels without adverse reactions were obtained with microemulsion cyclosporine. Doses of cyclos porine need not to be changed during the conversion

Calcioantagonistas en gineco-obstetricia / Calcium antagonists in gynecobstetrics

Los calcioantagonistas tiene una serie de efectos sobre la musculatura lisa de los vasos y también sobre otra musculatura lisa como es la del útero. En el presente trabajo se revisa la farmacología de los diferentes agentes así como sus efectos sobre el útero y el feto. También se plantea los usos que pueden tener estos agentes y su rol en una patología importante de la gestación, como es la hipertensión.

Effect of nitrendipine, nimodipine and nisoldipine on water and electrolytes excretion in rats.

In water loaded (5 ml/100 g) unanesthetized rats. nitrendipine (NT), nimodipine (NM) and nisoldipine (NS) (5 mg/ kg, i.p.) caused significant (P < 0.01) increase in water and Na+ excretion. However, there was no significant increase in K+ excretion after NT, NM and NS administration. NS was more potent in increasing excretion of water load as compared to NT and NM. The glomerular filtration rate as assessed by creatinine clearance, was significantly (P < 0.01) increased in NT, NM and NS (5 mg/kg, i.p.) treated groups as compared to control. The mean creatinine clearance values after NT, NM and NS were 26.95 +/- 0.35, 22.11 +/- 0.72 and 28.13 +/- 0.95 respectively as compared to 22.19 +/- 0.51, 18.77 +/- 0.42 and 22.97 +/- 0.60 in corresponding control groups. The results of the study suggest that in addition to other effects, NT, NM and NS have a selective inhibitory effect on Na+ handling mechanisms in the nephron.

Protection of CCL4-induced liver damage in rats by some calcium channel blockers.

Liver necrosis was produced in rats by administering 3 doses o a mixture o carbon tetrachloide+olive oil, 2 ml/kg, ip. The liver damage was evidenced by the elevated levels serun aspartate aminotrans ferase (AST), alanine aminotransferase (AIT) and gamma glutamyl transpeptidase (gamma-GT) and by histopathological observations of liver sections. Nitrendipine, nimodipine and nisoldipine (1 mg/100 g of rat, ip) significantly reduced these elevated levels of AST, AIT and gamma-GT. Carbon tetrachloride induced liver necrosis was also found to be significantly reduced in nitrendipine, nimodipine and nisoldipine pre-treated animals as observed macroscopically and histologically.

Effect of nitrendipine, nimodipine and nisoldipine on experimentally induced myocardial infarction in rats.

Cardiac necrosis was produced in rats by administering isoproterenol sulphate (85 mg/kg, sc for 4 days). The myocardial damage was proved by observing the elevated levels of serum aspartate aminotransferase, ++alanine aminotransferase and lactate dehydrogenase and the changes were confirmed by his topathology. Nitrendipine, nimodipine and nisoldipine (10 mg/kg, ip) significantly reduced the elevated levels of these enzymes. The average degree of cardiac necrosis in these rats when observed microscopically and histologically was also found to be significantly reduced on pretreatment with these drugs. Nisoldipine was more effective in preventing cardiac necrosis as compared to nitrendipine and nimodipine.