Effects Of Isradipine Research Articles

Neuromodulatory Inputs to Motoneurons Contribute to the Loss of Independent Joint Control in Chronic Moderate to Severe Hemiparetic Stroke.

In chronic hemiparetic stroke, increased shoulder abductor activity causes involuntary increases in elbow, wrist, and finger flexor activation, an abnormal muscle coactivation pattern known as the flexion synergy. Recent evidence suggests that flexion synergy expression may reflect recruitment of contralesional cortico-reticulospinal motor pathways following damage to the ipsilesional corticospinal tract. However, because reticulospinal motor pathways produce relatively weak post-synaptic potentials in motoneurons, it is unknown how preferential use of these pathways could lead to robust muscle activation. Here, we hypothesize that the descending neuromodulatory component of the ponto-medullary reticular formation, which uses the monoaminergic neurotransmitters norepinephrine and serotonin, serves as a gain control mechanism to facilitate motoneuron responses to reticulospinal motor commands. Thus, inhibition of the neuromodulatory component would reduce flexion synergy expression by disfacilitating spinal motoneurons. To test this hypothesis, we conducted a pre-clinical study utilizing two targeted neuropharmacological probes and inert placebo in a cohort of 16 individuals with chronic hemiparetic stroke. Test compounds included Tizanidine (TIZ), a noradrenergic α2 agonist and imidazoline ligand selected for its ability to reduce descending noradrenergic drive, and Isradipine, a dihyropyridine calcium-channel antagonist selected for its ability to post-synaptically mitigate a portion of the excitatory effects of monoamines on motoneurons. We used a previously validated robotic measure to quantify flexion synergy expression. We found that Tizanidine significantly reduced expression of the flexion synergy. A predominantly spinal action for this effect is unlikely because Tizanidine is an agonist acting on a baseline of spinal noradrenergic drive that is likely to be pathologically enhanced post-stroke due to increased reliance on cortico-reticulospinal motor pathways. Although spinal actions of TIZ cannot be excluded, particularly from Group II pathways, our finding is consistent with a supraspinal action of Tizanidine to reduce descending noradrenergic drive and disfacilitate motoneurons. The effects of Isradipine were not different from placebo, likely related to poor central bioavailability. These results support the hypothesis that the descending monoaminergic component of the ponto-medullary reticular formation plays a key role in flexion synergy expression in chronic hemiparetic stroke. These results may provide the basis for new therapeutic strategies to complement physical rehabilitation.

Gebe ratlarda isradipinin uterus kontraksiyonları üzerine inhibitör etkileri

Gebe ratlarda isradipinin uterus kontraksiyonları üzerine inhibitör etkileri

The effect of isradipine in acute altitude hypoxia on cerebral, renal, and splanchnic blood flow evaluated by Doppler measurements

Recent studies have suggested that calcium antagonists may have a beneficial effect on high altitude pulmonary edema, but the effect on regional blood flow distribution is unknown. This study by transcranial and duplex Doppler evaluated the effect of the calcium antagonist isradipine on cerebral, renal, and splanchnic blood flows in acute altitude hypoxia. Twelve healthy subjects were investigated at sea level and repeatedly after 3–56 hours at high altitude (4350 m). Before the ascent, the subjects were randomized to treatment with isradipine 5 mg/day (n=6) or placebo (n=6). We measured flow velocities in middle cerebral arteries; flow rates in internal carotid arteries, portal vein, and right renal artery; and resistance indices in middle cerebral, internal carotid, renal, superior mesenteric, and hepatic arteries. Hypoxia increased middle cerebral artery flow velocity by 30% (placebo,p<0.05) and 39% (isradipine,p<0.01); increased internal carotid artery flow rate by 57% (placebo,p<0.01) and 55% (isradipine,p<0.05); and decreased middle cerebral and internal carotid artery resistance indices without differences between placebo and isradipine groups. Superior mesenteric artery resistance index was lower in hypoxia with isradipine compared with placebo (p<0.05), suggesting a higher splanchnic blood flow. In conclusion, acute hypoxia induced an increase in cerebral blood flow. Besides decreasing superior mesenteric artery resistance index, prophylactic isradipine did not modulate the circulatory responses to acute hypoxia. The clinical significance of this increased splanchnic blood flow remains unclear.

Isradipine antagonizes hypobaric hypoxia induced CA1 damage and memory impairment: Complementary roles of L-type calcium channel and NMDA receptors

Hypobaric hypoxia leads to cognitive dysfunctions due to increase in intracellular calcium through ion channels. The purpose of this study was to examine the temporal contribution of L-type calcium channels and N-methyl-D-aspartate receptors (NMDARs) in mediating neuronal death in male Sprague Dawley rats exposed to hypobaric hypoxia simulating an altitude of 25,000 ft for different durations. Decreasing exogenous calcium loads by blocking voltage-gated calcium influx with isradipine (2.5 mg kg − 1 ), and its efficacy in providing neuroprotection and preventing memory impairment following hypoxic exposure was also investigated. Effect of isradipine on calcium-dependent enzymes mediating oxidative stress and apoptotic cell death was also studied. Blocking of L-type calcium channels with isradipine reduced hypoxia-induced activation of calcium dependent xanthine oxidases, monoamine oxidases, cytosolic phospholipase A 2 and cycloxygenases (COX-2) along with concomitant decrease in free radical generation and cytochrome c release. Increased expression of calpain and caspase 3 was also observed following exposure to hypobaric hypoxia along with augmented neurodegeneration and memory impairment which was adequately prevented by isradipine administration. Administration of isradipine during hypoxic exposure protected the hippocampal neurons following 3 and 7 days of exposure to hypobaric hypoxia along with improvement in spatial memory.

2.256 The effect of isradipine on Parkinson's disease: A retrospective study in Korea

2.256 The effect of isradipine on Parkinson's disease: A retrospective study in Korea

Protective effects of a calcium channel blocker on apoptosis in thymus of neonatal STZ-diabetic rats

Streptozotocin (STZ) is known to induce insulin-dependent diabetes in experimental animals. In STZ-induced diabetes, atrophy of the thymus is caused by elevated intracellular calcium levels leading to apoptosis. Hyperglycemia is known to result in a decrease in numbers of T cells in the thymus and circulation. Intracellular calcium levels increase in diabetic animals after induction by STZ. Hyperglycemia inhibits Ca2+-ATPase and increases intracellular calcium levels. We have investigated apoptosis in thymus tissue of neonatal STZ (n-STZ)-diabetic rats and the effects of isradipine as a calcium channel blocker (CCB) on apoptosis. Five groups of newborn Wistar rats were used. On the second day after birth, 100 mg/kg STZ was given i.p. to the first two groups. The first group was n-STZ diabetic. To the second group, starting from the 12th week, 5 mg/kg/day isradipine (i.p) was given for 6 weeks. To the third group, the same dose of isradipine was given on the second day, followed by STZ treatment. The fourth group was non-diabetic and treated with 5 mg/kg/day isradipine for six weeks. The fifth group consisted of non-diabetic rats. To the sixth group, dexamethasone (5 mg/kg i.p.) was given to adult rats. For detection of apoptotic cells in paraffin-embedded thymus sections, the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay was used. The DNA ladder method was performed for analysis of DNA fragmentation. In the isradipine-treated non-diabetic group, typical apoptotic banding patterns were found, whereas thick bands between 123 and 246 bp length were found in the n-STZ- and n-STZ+isradipine-treated groups. More apoptotic cells were observed in the thymus of isradipine-treated, n-STZ-treated and n-STZ+isradipine-treated groups when compared with the non-diabetic control and isradipine+n-STZ-treated groups. In conclusion, we observed that long-term STZ diabetes results in apoptosis in the thymus. We also found that isradipine administered before STZ has protective effects against apoptosis, whereas isradipine alone induces apoptosis.

Effects of isradipine, a dihydropyridine-class calcium-channel antagonist, on d-methamphetamine's subjective and reinforcing effects

In healthy human volunteers, we have previously shown that isradipine, a dihydropyridine-class calcium-channel antagonist, reduces some methamphetamine-induced positive subjective effects associated with its abuse liability, presumably by antagonizing cortico-mesolimbic dopamine pathways. In the present study, we combined acute immediate-release (IR) isradipine with repeated sustained-release (SR) isradipine pretreatment to determine whether isradipine could antagonize methamphetamine's positive subjective and reinforcing effects in methamphetamine-dependent research subjects. We included 18 non-treatment-seeking, methamphetamine-dependent subjects aged between 18 and 51 years in this double-blind, within-subject, cross-over study, which was done in a human laboratory. Intravenous methamphetamine (0, 15 and 30 mg) was administered on three different days after 5 days of double-blind cross-over treatment with either isradipine or matching placebo. Subjects received oral isradipine 30 mg SR at bedtime, plus 15 mg IR administered 2 h before methamphetamine infusion. Self-report questionnaires measured drug liking, euphoria, craving, stimulation, and methamphetamine preference. Methamphetamine reinforcement was measured by a behavioural procedure involving choices between methamphetamine and money. For those who received isradipine second and placebo first as the pretreatment paradigm but not vice versa, methamphetamine-induced drug liking, elation, and preference were reduced significantly by isradipine. Depending upon conditioning status, isradipine can reduce some methamphetamine-induced positive subjective and reinforcing effects associated with its abuse liability in methamphetamine addicts.

Effects of isradipine on cocaine-induced changes in cognitive performance in recently abstinent cocaine-dependent individuals

Recently abstinent cocaine-dependent individuals, compared with healthy controls, appear more likely to exhibit deficits in cognitive performance and attention. Individuals with such cognitive deficits might be less able to avail themselves of rehabilitative or relapse-prevention efforts. Pharmacotherapy that reduces the impairment in cognitive performance among cocaine-dependent individuals would be a useful clinical tool. Preclinical and human studies suggest that the dihydropyridine-class calcium-channel antagonist, isradipine, can enhance neurocognitive function in some neuropsychiatric disorders. Isradipine, presumably by increasing cerebral blood flow and its actions at various neurotransmitter systems, might, therefore, ameliorate the impairment in cognitive performance and attention seen in cocaine addicts and enhance the expected modest improvement in performance during acute cocaine-taking in these same individuals. Among 12 male and female cocaine-dependent individuals, we examined the effects of low and high doses of intravenous cocaine (0, 0.325, and 0.650 mg/kg) on cognitive performance and attention in both the presence and absence of isradipine (0 or 30 mg sustained release each evening prior to testing, plus 0 or 15 mg immediate release each morning 2 h before the cocaine or placebo cocaine infusion and on the day of testing). Intravenous cocaine produced a modest increase in cognitive performance and attention. Isradipine, both with and without cocaine, had no effect on these same parameters. Hence, cocaine-taking by cocaine-dependent individuals produces little improvement in cognitive performance and attention in either the presence or absence of isradipine.

Isradipine prevents the development of spontaneously occurring cardiac necrosis in cardiomyopathic hamster.

Recent studies on the heart necrotizing process at the early stages of hamster polymyopathy have led us to believe that this hereditary disease derives from an anomalous transmembrane ion flux due to the presence of slow Na+ channels that contribute to intracellular Na+ accumulation which promote intracellular Ca2+ overload via the Ca2+ influx through the Na+-Ca2+ exchanger. In the present study, we investigated the potential beneficial effect of chronic treatment with a dual L-type Ca2+ and slow Na+ channel blockers isradipine, on the development of necrosis in myopathic hamster hearts. Young cardiomyopathic (CM) hamsters (CMH) were treated with isradipine (0.1 mg x kg(-1) x day(-1)) and nifedipine (1 mg x kg(-1) x day(-1)) for 4 consecutive weeks. Microscopic assessments were carried out in staged serial paraffin sections of heart ventricles from tissues freshly dissected at autopsy. In comparison with control nontreated hearts, which exhibited numerous necrotic calcific foci, myolytic lesions, and dilated right ventricle, isradipine treatment prevented, in a significant manner, all the above spontaneous pathological changes, while nifedipine had no effect. Our present observations provide evidence for the first time that in vivo treatment with a DHP Ca2+ channel blocker, isradipine, is cardioprotective against the development of necrosis in hereditary cardiomyopathy in the hamster. It is possible that the protective effect of isradipine in CMH could be largely due to the indirect blockade of Ca2+ influx through the Na+-Ca2+ exchanger as well as to possible direct blockade of Ca2+ influx through the T-type Ca2+ channel.

The effects of isradipine during and after coronary artery bypass surgery

The effects of isradipine during and after coronary artery bypass surgery

Effects of isradipine or enalapril on blood pressure in salt-sensitive hypertensives during low and high dietary salt intake

This large multicenter study, tested the antihypertensive effects of isradipine, a dihydropyridine calcium channel blocker and enalapril, an angiotensin-converting enzyme inhibitor, in salt-sensitive hypertensive patients under low and high salt intake diets. After a 3-week (weeks −9 to −6) of ad lib salt diet, those patients who had a sitting diastolic blood pressure (SDBP) of ≥95 but ≤115 mm Hg qualified to enter a 3-week (weeks −6 to −3) placebo run-in low salt diet (50 to 80 mmol Na + /day). Then high salt (200 to 250 mmol Na + /day) was added to the placebo treatment for 3 weeks (weeks −3 to 0). Those patients who demonstrated an increase in SDBP ≥5 mm Hg from the low to high salt diet were considered salt sensitive and were randomized into a 4-week (weeks 0 to 4) double-blind treatment period of either isradipine 2.5 to 10 mg twice a day, enalapril 2.5 to 20 mg twice a day, or placebo. Then they entered a 3-week (weeks 4 to 7) placebo washout phase of low salt diet (50 to 80 mmol Na + /day). After week 7 and while the low salt diet was continued the patients were restarted on their double-blind treatment for 4 more weeks (weeks 7 to 11) and the study was completed. Of 1916 patients screened, 464 were randomized into the double-blind treatment phase and 397 completed the study. Both isradipine and enalapril decreased the sitting systolic blood pressure (SSBP) and SDBP during the high salt diet, to a similar degree, whereas enalapril caused a greater reduction in SSBP and SDBP than isradipine during the low salt diet (11.3 ± 1.2/7.7 ± 0.7 mm Hg v 7.7 ± 0.9/4.8 ± 0.6 mm Hg, mean ± SEM, respectively, P < .02). Within drugs, the effect of isradipine on blood pressure (BP) was higher during the high than the low salt diet (14.9 ± 1.5 v 7.6 ± 1.3 mm Hg for SSBP and 10.1 ± 0.6 v 4.8 ± 0.9 mm Hg for SDBP, P < .001), but enalapril exerted a similar effect during both diets. Because salt restriction lowered both SSBP and SDBP, the lowest BP achieved with both drugs were during the salt restriction phase.

Effects of Isradipine, a Dihydropyridine-Class Calcium Channel Antagonist, on D-Methamphetamine-Induced Cognitive and Physiological Changes in Humans

D-methamphetamine is abused for its euphoric effects and stimulatory action on cognitive function. Its abuse can, however, be associated with massive hypertension resulting in strokes, ruptured aneurysms, or myocardial infarction. We examined the utility of isradipine, a dihydropyridine-class calcium channel antagonist, in treating d-methamphetamine induced hypertension and evaluated its effects on cognitive function, both of which are mediated by dopaminergic mechanisms. D-methamphetamine dose-dependently increased all vital signs (systolic, diastolic, and mean arterial pressure, and pulse rate) parameters. Isradipine significantly reduced d-methamphetamine-induced increases in diastolic and mean arterial pressure; however, this potentially beneficial therapeutic effect was offset by a significant reflex rise in pulse rate. D-methamphetamine also improved attention, accuracy of reasoning ability, and performance on computerized cognitive function tasks. D-methamphetamine's cognitive improving effects were not altered significantly by isradipine. Isradipine increased the false responding rate but was without significant effect on any other attentional task, or on reasoning ability, or performance. Isradipine does not appear to enhance cognitive function in healthy humans.

Hypertension after liver transplantation: A predictive role for pretreatment hemodynamics and effects of isradipine on the systemic and renal circulations

Hypertension developing after liver transplantation during immunosuppression with cyclosporine A reflects an unusual hemodynamic transition from peripheral vasodilation to systemic and renal vasoconstriction. Although dihydropyridine calcium channel blockers are often administered for their efficacy in promoting vasodilation, some liver transplant recipients report marked symptomatic intolerance to these agents. In the present study we examined systemic and renal responses to isradipine using systemic (thoracic bioimpedance) and renal hemodynamic measurements in 15 liver transplant recipients studied at the time of initial diagnosis of posttransplant hypertension and after 3 months of treatment. Circadian blood pressure patterns were examined by overnight ambulatory blood pressure monitoring before and during antihypertensive therapy. During isradipine administration, blood pressure decreased from 151 ± 3/91 ± 2 to 130 ± 3/81 ± 2 mm Hg ( P < .01) without change in renal blood flow (406 ± 43 to 425 ± 52 mL/min/1.73m 2, P = NS) or renal vascular resistance index (25,674 ± 3312 to 20,520 ± 2311 dynes · sec · cm −5/m 2, P = NS). Pre-treatment differences in systemic vascular tone persisted during treatment and predicted the tendency for symptomatic tachycardia and flushing, predominantly in those with hyperdynamic circulations. Twice daily dosing of isradipine was associated with partial and significant restoration of the nocturnal decrease in blood pressure (systolic blood pressure decreased 5.5%, normal 13%), usually absent early after transplantation. Our results demonstrate the ability of hemodynamic measurements to predict the symptomatic response to antihypertensive therapy in the posttransplant setting.

Effects of isradipine on intravenous cocaine-induced cardiovascular response: a pilot study

Effects of isradipine on intravenous cocaine-induced cardiovascular response: a pilot study

Alteration of rat cerebral microvascular eicosanoid formation by isradipine, a calcium channel blocker

We studied the influence of the calcium channel blocker isradipine on cerebral microvascular and aortic eicosanoid synthesis. The rat cerebral microvascular eicosanoid formation was assessed by means of bioassay, radioimmunoassay and radio thin layer chromatography from endogenous as well as from exogenous (20:4) radiolabelled substrate. The in vitro as well as the in vivo (0.3 mg/kg/day for 1 week) effect of isradipine was examined. Isradipine increased significantly ( P < 0.01) both conversion to and formation of PGI 2 and its derivative 6-oxo-PGF 1α, respectively, as well as PGD 2-production, while TXB 2-synthesis was diminished. The conversion to the other metabolites was not affected to a significant extent. These findings indicate that isradipine enhances PGI 2-generation in aorta and cerebral microvessels from both exogenous and endogenous substrate and PGD 2 from endogenous substrate, a phenomenon shown to underlie the antiatherosclerotic actions of this calcium channel blocker.

Effects of Isradipine, an L-Type Calcium Channel Blocker on Permanent and Transient Focal Cerebral Ischemia in Spontaneously Hypertensive Rats

Permanent or transient focal cerebral ischemia was induced in spontaneously hypertensive rats (SHR) using the intraluminal filament method. Successful occlusion of the middle cerebral artery (MCA) was achieved using 4/O filaments (terminal diameter 0.20-0.25 mm) coated with poly-L-lysine. The L-type calcium channel blocker isradipine (2.5 mg/kg) administered subcutaneously 30 min following permanent MCA occlusion significantly reduced the volume of ischemic brain damage in the cerebral hemisphere (25%; P = 0.0001), cerebral cortex (18%; P = 0.0034), and caudate nucleus (33%; P = 0.0002) when assessed at 24 h post-MCA occlusion. Isradipine did not affect the functional deficit (measured using a subjective neurological scoring system) induced by MCA occlusion. In SHR undergoing transient (2 h) MCA occlusion isradipine administered 30 min post-MCA occlusion produced a significant reduction (47%; P = 0.001) in hemispheric infarct volume, whereas isradipine administered at the onset of reperfusion did not confer any significant neuroprotection. No change in functional deficit was seen with isradipine with either dosing paradigm at 24 h post-MCA occlusion. These results demonstrate that the intraluminal filament method of MCA occlusion can be used in the SHR strain and also substantiates the neuroprotective efficacy of isradipine in SHR models of permanent and transient focal cerebral ischemia.

Interactions Between Darodipine or Isradipine and the 5-HT 1A Receptor Agonist 8-OHDPAT in Rat Brain

Isradipine and darodipine are dihydropyridine calcium antagonists that affect the serotonergic pathways with a peculiar profile of effects because, at low dose (0.08 and 0.3 mg/kg, respectively) they facilitate, but at high dose (1.60 and 5.0 mg/kg, respectively) they inhibit the serotonergic neurotransmission. To investigate the mechanisms of these effects, the selective 5-HT 1A receptor agonist 8-OHDPAT was injected SC to rats pretreated IP with isradipine (0.04–1.60 mg/kg) or darodipine (0.3–5.0 mg/kg). By stimulating presynaptic 5-HT 1A autoreceptor, 8-OHDPAT induced signs of inhibition of the serotonergic neutransmission (i.e., decrease of the 5-HIIA/5-HT ratio), but it also produced behavioral effects by stimulating postsynaptic 5-HT 1A receptors (i.e., forepaw treadings). A low dose of isradipine (0.08 mg/kg) or darodipine (0.3 mg/kg) antagonized the presynaptic, but enhanced the postsynaptic effects of 8-OHDPAT, suggesting relief of the autoreceptor-mediated inhibition of the 5-HT release. Thus, the amine released could stimulate postsynaptic receptors, adding its action to that of 8-OHDPAT. A high dose of isradipine (1.60 mg/kg) or darodipine (5.0 mg/kg) left unchanged, or also enhanced, the signs of inhibition of serotonergic neurotransmission displayed by 8-OHDPAT, reducing but not suppressing the increase in the behavioral response to the stimulation of postsynaptic 5-HT 1A receptors. It was speculated that the effects of isradipine and darodipine on serotonergic pathways of rat brain could be due to changes in the back-regulation of the neurotransmission, mediated by 5-HT 1A autoreceptors. This mechanism of action could be extended to other dihydropyridine calcium antagonists, because blockade of L-type VSCC by these compounds appears to be involved in their effects on brain 5-HT turnover.

Effect of isradipine, a dihydropyridine-calcium antagonist on I.V. self-administration of morphine in rats

The effect of dihydropyridine calcium channel antagonist isradipine (PN 200-110) on morphine reinforcement has been investigated using i.v. self-administration test in rats. Rats were given the opportunity to self-administer a solution of morphine (1 mg/Ml, i.v.) in a 1 hr limited access paradigm (FR = 1). Within 5–7 days rats had learned to self-administer approximately 1 mg of morphine in 1 hr as evidenced by a plateau of responding. The administration of isradipine (1.2, 2.5 and 5.0 mg/kg s.c.) 90 min before the morphine self-administration session, induced dose-dependent increase in the number of morphine self-infusions with respect to basal values. This response pattern was very similar to the one observed when morphine solution was substituted by saline in trained rats not treated with isradipine. The results indicate that isradipine inhibits partially the reinforcing properties of morphine in self-administration test.

Isradipine inhibits nicotine intravenous self-administration in drug-naive mice

The effect of isradipine, a dihydropyridine calcium antagonist, on intravenous self-administration of nicotine in naive mice has been investigated. When nicotine injections were made contingent upon nose-poke response by naive mice, they increased their rate of nose poking with respect to animals receiving contingent saline injections or yoked control animals receiving noncontingent nicotine injections. Pretreatment of mice with mecamylamine (2.4 mg/kg) inhibited self-administration of nicotine contingent upon a nose-poke response. The same effect was observed with isradipine (0.5–1.0 mg/ kg) in a dose-related manner and stereospecifically. These data suggest that isradipine suppresses the reinforcing properties of nicotine and might be useful for treatment of nicotine abuse.

The effect of isradipine in acute altitude hypoxia on cerebral, renal, and splanchnic blood flow evaluated by Doppler measurements

Recent studies have suggested that calcium antagonists may have a beneficial effect on high altitude pulmonary edema, but the effect on regional blood flow distribution is unknown. This study by transcranial and duplex Doppler evaluated the effect of the calcium antagonist isradipine on cerebral, renal, and splanchnic blood flows in acute altitude hypoxia. Twelve healthy subjects were investigated at sea level and repeatedly after 3–56 hours at high altitude (4350 m). Before the ascent, the subjects were randomized to treatment with isradipine 5 mg/day (n = 6) or placebo (n = 6). We measured flow velocities in middle cerebral arteries; flow rates in internal carotid arteries, portal vein, and right renal artery; and resistance indices in middle cerebral, internal carotid, renal, superior mesenteric, and hepatic arteries. Hypoxia increased middle cerebral artery flow velocity by 30% (placebo, p < 0.05) and 39% (isradipine, p < 0.01); increased internal carotid artery flow rate by 57% (placebo, p < 0.01) and 55% (isradipine, p < 0.05); and decreased middle cerebral and internal carotid artery resistance indices without differences between placebo and isradipine groups. Superior mesenteric artery resistance index was lower in hypoxia with isradipine compared with placebo (p < 0.05), suggesting a higher splanchnic blood flow. In conclusion, acute hypoxia induced an increase in cerebral blood flow. Besides decreasing superior mesenteric artery resistance index, prophylactic isradipine did not modulate the circulatory responses to acute hypoxia. The clinical significance of this increased splanchnic blood flow remains unclear.