Oral Nicardipine Research Articles

Hypoxia Associated With Dihydropyridine Calcium Channel Inhibitors: A Pharmacovigilance Study in VigiBase.

Due to their negative effects on hypoxic pulmonary vasoconstriction, dihydropyridine calcium channel inhibitors (DCCIs) can lead to hypoxia in patients with a pulmonary shunt. To date, only preclinical studies and case reports have focused on this potential adverse drug reaction. We aimed to assess the reporting association between DCCIs and hypoxia using the World Health Organization pharmacovigilance database (VigiBase). We performed a disproportionality analysis to evaluate the strength of the reporting association between i.v. clevidipine and nicardipine, thought to be a surrogate of patients in the intensive care unit, and hypoxia. The information component and the lower end of its 95% credibility interval were used to evaluate disproportionality. A description of the cases was made. Secondary outcomes included the association between all DCCIs and hypoxia compared with other treatments with similar indications, urapidil and labetalol, regardless of the route of administration. Association between oral nicardipine and hypoxia was also searched. A statistically significant signal of hypoxia was found for intravenous clevidipine and nicardipine. The time to onset was reported with a median of 2 days (interquartile range 1.5-4.5). Four dechallenges were performed with intravenous nicardipine, leading to the resolution of the symptoms. Regardless of the route of administration, a signal of hypoxia was also found for nimodipine but not for other drugs, including comparators. For nicardipine no signal of hypoxia was found with the oral route of administration. Our pharmacovigilance database analysis showed a significant association between the use of intravenous DCCIs and hypoxia.

Mechanisms of the antihypertensive effects of Nigella sativa oil in L-NAME-induced hypertensive rats

OBJECTIVESThis study was conducted to determine whether the blood pressure-lowering effect of Nigella sativa might be mediated by its effects on nitric oxide, angiotensin-converting enzyme, heme oxygenase and oxidative stress markers.METHODS:Twenty-four adult male Sprague-Dawley rats were divided equally into 4 groups. One group served as the control (group 1), whereas the other three groups (groups 2-4) were administered L-NAME (25 mg/kg, intraperitoneally). Groups 3 and 4 were given oral nicardipine daily at a dose of 3 mg/kg and Nigella sativa oil at a dose of 2.5 mg/kg for 8 weeks, respectively, concomitantly with L-NAME administration.RESULTSNigella sativa oil prevented the increase in systolic blood pressure in the L-NAME-treated rats. The blood pressure reduction was associated with a reduction in cardiac lipid peroxidation product, NADPH oxidase, angiotensin-converting enzyme activity and plasma nitric oxide, as well as with an increase in heme oxygenase-1 activity in the heart. The effects of Nigella sativa on blood pressure, lipid peroxidation product, nicotinamide adenine dinucleotide phosphate oxidase and angiotensin-converting enzyme were similar to those of nicardipine. In contrast, L-NAME had opposite effects on lipid peroxidation, angiotensin-converting enzyme and NO.CONCLUSION:The antihypertensive effect of Nigella sativa oil appears to be mediated by a reduction in cardiac oxidative stress and angiotensin-converting enzyme activity, an increase in cardiac heme oxygenase-1 activity and a prevention of plasma nitric oxide loss. Thus, Nigella sativa oil might be beneficial for controlling hypertension.

Utility of oral nicardipine and magnesium sulfate infusion during preparation and resection of pheochromocytomas

Calcium channel blockade with nicardipine (NC) is an alternative to phenoxybenzamine (PB) preparation for resection of a pheochromocytoma. Intraoperative magnesium sulfate infusion (+MgSO(4)) is often used for its cardiovascular stabilizing properties. We hypothesized that preparation with NC would be similar clinically to PB for resection of a pheochromocytoma, and MgSO(4) infusion would not affect intraoperative stability. This retrospective review included 64 patients undergoing resections of a pheochromocytoma from 2003 to 2011. PB or NC was used preoperatively, with MgSO(4) use distributed equally in the population. Pre-, intra-, and postoperative hemodynamics and outcomes were compared. There was no difference in NC (n = 7) versus PB (n = 57) or +MgSO(4) (n = 33) versus -MgSO(4) (n = 31) groups for demographics with the exception of age. The NC group had smaller median tumor size and lesser plasma baseline levels of normetanephrine than the PB group, but subgroup analysis of all neoplasms <3.0 cm revealed no differences. Pre-, intra- and postoperative hemodynamic stability and outcomes were similar for NC versus PB analyses as well as the +MgSO(4) versus -MgSO(4) groups. NC use may be an equivalent alternative to PB in preoperative preparation, especially for smaller pheochromocytomas. Intraoperative MgSO(4) use does not seem to have a substantive effect on hemodynamic stability.

Effects of lovastatin on the pharmacokinetics of nicardipine in rats

It has been reported that both nicardipine and lovastatin are substrates of both the cytochrome P450 (CYP) 3A subfamily and P-glycoprotein (P-gp), and P-gp transport is unlikely to be a significant factor. Thus, the effects of oral lovastatin on the pharmacokinetics of intravenous and oral nicardipine were investigated in rats. Nicardipine was administered intravenously (4 mg/kg) and orally (12 mg/kg) with 0 (control), 0.3 and 1 mg/kg of oral lovastatin to rats. Lovastatin was administered 30 min before nicardipine administration. After intravenous administration of nicardipine with 0, 0.3 and 1 mg/kg of lovastatin, the total areas under the plasma concentration-time curve from time zero to infinity (AUCs) of nicardipine were not changed by lovastatin. However, after oral administration of nicardipine with 1 mg/kg of oral lovastatin, the AUC of nicardipine was significantly greater (by 67.4%), and the extent of absolute oral bioavailability (F) of nicardipine was increased (by 38.5%). The above data suggest that lovastatin did not considerably inhibit the metabolism of nicardipine via the hepatic CYP3A subfamily, but inhibited intestinal P-gp and/or the CYP3A subfamily.

Effects of oral epigallocatechin gallate on the pharmacokinetics of nicardipine in rats

Epigallocatechin gallate (EGCG), irreversibly inhibits cytochrome P450 (CYP) 3A subfamily and P-glycoprotein (P-gp) in vitro. This study investigated the effect of oral EGCG on the pharmacokinetics of intravenous and oral nicardipine in rats. Nicardipine was administered orally (12 mg/kg) or intravenously (4 mg/kg) with or without oral EGCG (0.5, 3 or 10 mg/kg) to rats. Compared to controls (without EGCG), the total areas under the plasma concentration-time curve (AUCs) of intravenous nicardipine were greater with oral EGCG. Compared to controls (without EGCG), the AUCs of oral nicardipine and the extent of absolute oral bioavailability (F) were also greater with oral EGCG. The above data suggest that oral EGCG inhibited both the hepatic CYP3A subfamily and intestinal P-gp.

Midodrine Improves Orgasm in Spinal Cord‐Injured Men: The Effects of Autonomic Stimulation

Orgasm is less frequent in men with spinal cord injury (SCI) than in able-bodied subjects, and is poorly understood. To assess the effect of autonomic stimulation on orgasm in SCI men using midodrine, an alpha1-adrenergic agonist agent. Penile vibratory stimulation (PVS) was performed in 158 SCI men on midodrine as part of a treatment for anejaculation, after they failed a baseline PVS. A maximum of four trials were performed, weekly, with increasing doses of midodrine. The presence and type of ejaculation, orgasm experiences, and cardiovascular data were collected. Ejaculation either antegrade or retrograde was obtained in 102 SCI men (65%). Orgasm without ejaculation was reported by 14 patients (9%) on baseline PVS. Ninety-three patients (59%) experienced orgasm during PVS on midodrine. Orgasm was significantly related to the presence of ejaculation in 86 patients (84%), and more strikingly to antegrade ejaculation (pure or mixed with retrograde), i.e., in 98% of 70 patients. Orgasm was significantly more frequent in patients with upper motor neuron and incomplete lesions who present somatic responses during PVS. There was no effect of the presence of psychogenic erection. There was a significant increase in both systolic and diastolic blood pressure. Sixteen patients, mainly tetraplegics, developed intense autonomic dysreflexia (AD) that required an oral nicardipine chlorhydrate. Orgasm is the brain's cognitive interpretation of genital sensations and somatic responses, AD, and ejaculation. Intact sacral and T10-L2 cord segments are mandatory, allowing coordination between internal and external sphincters. Autonomic stimulation with midodrine enhances orgasm rate, mainly by creating antegrade ejaculation.

A rare case of labetalol induced hepatic necrosis

Labetalol is an anti-hypertensive agent useful through the spectrum of hypertensive emergencies, urgencies, and chronic therapy. It has a rare side effect of hepatotoxicity with hepatic necrosis. Only eleven known cases are reported in the literature. A 47-year-old African American female presented with severe hypertension, blood pressure 210/110. She was previously uncontrolled on diltiazem and had significant past medical history of methyldopa induced hepatitis 15 years prior. She was started on labetalol at standard doses with upward gradual titration. Eight weeks later HCTZ was added. Approximately three months post initiation of labetalol, the patient presented to the clinic with painless jaundice associated with very high liver enzymes, and BP of >300/130. Extensive inpatient testing excluded infectious hepatitis and autoimmune hepatitis. Liver enzymes showed incomplete downward trend off HCTZ. ACEI and spironolactone were added, and the BP improved to 150/90. The patient was followed in clinic for two weeks due to investigating an elevated CA 19-9 and possible mass at the pancreatic head on CT abdomen. She was readmitted as an inpatient for accelerated HTN with BP of 230/130, rising liver enzymes, and jaundice. Upon admission all home meds were discontinued. Liver biopsy excluded neoplasm but revealed bridging hepatocyte necrosis. The blood pressure was controlled with oral nicardipine. The patients’ condition regressed to fulminant hepatic failure, hepatic encephalopathy, and acute renal failure. She required a liver transplant and now is stable eight months post liver transplant. Labetalol hepatotoxicity and hepatic necrosis is a potentially life threatening illness, which can result in hepatic failure and multi-organ failure necessitating liver transplantation. Routine surveillance of liver enzymes may become necessary for a subset of high risk patients on chronic labetalol therapy.

OCCUPANCY BY ORAL ADMINISTRATION OF NICARDIPINE OF L-TYPE CALCIUM CHANNELS IN RAT BRAIN

The occupancy of L-type Ca2+ channels by treatment with an oral dose of the dihydropyridine-type Ca2+ antagonist nicardipine (sustained-release formulation) was evaluated in membrane preparations of rat frontal cortex and hippocampus using a radioligand binding assay technique, with [3H]-nicardipine as a ligand. Three hours after nicardipine administration, specific binding was decreased by about 15–20%, both in the frontal cortex and hippocampus. This indicates that oral nicardipine occupied approximately 15–20% of L-type Ca2+ channels. A progressive occupancy of Ca2+ channels was observed between six and 12 h after nicardipine administration. Twelve hours after drug administration, approximately 65–70% of Ca2+ channels were occupied.These findings indicate that oral treatment with 3 mg/kg of nicardipine (sustained-release formulation) occupies L-type Ca2+ channels in rat brain by more than 40% from the 6th to the 24th h after drug administration. This suggests that an oral dose of nicardipine (sustained-release formulation) induces a significant occupancy of L-type Ca2+ channels in rat frontal cortex and hippocampus for about one day. The possible clinico-therapeutic relevance of this observation is discussed.

Arteritis cerebral e involución psíquica en el niño. Presentación de un caso con buena respuesta al tratamiento

To show the importance of the cerebral arteritis as etiology of the language and the intellectual involution in children. A boy started to show psychic and language involution since 18 months of life to arrive to an autistic behavior. After showing normal results in all the studies performed in order to investigate the possible etiologies, cerebral arteriography was performed. Cerebral arteritis affecting especially the right opercular artery was disclosed. Oral nicardipine administration was follow-up of a complete recuperation. Cerebral arteritis is very seldom managed as the cause of intellectual and/or language involution in children as it also occurs with the syndrome of acquired aphasia. However, this pathology has a good response not only to corticoids but also to calcium channel antagonists as it occurred in our patient.

Oral nicardipine versus intravenous magnesium sulfate for the treatment of preterm labor

Objective: The aim of this study was to compare the efficacy and safety of oral nicardipine in acute therapy for preterm labor with those of parenteral magnesium sulfate. Study Design: Patients between 24 and 34 weeks’ gestation with documented preterm labor were randomly assigned to receive oral nicardipine (n = 57) or intravenous magnesium sulfate (n = 65) as initial tocolytic therapy. Patients in the nicardipine group received a 40-mg loading dose and then 20 mg every 2 hours as needed to stop contractions (total 80 mg). Patients in the magnesium sulfate group received a 6-g bolus followed by 2 to 4 g/h to provide uterine quiescence. Patients could be switched to another tocolytic regimen if they continued to have contractions after 6 hours of therapy. The main outcome variables examined were time to uterine quiescence, time gained in utero, recurrence of preterm labor, failure of tocolysis, and pertinent maternal and neonatal outcomes. Results: There were no significant differences in maternal demographic characteristics between the groups. Among patients who responded with uterine quiescence within 6 hours, there was a significant decrease in the time to uterine quiescence in the nicardipine group (P < .01). Patients in the magnesium sulfate group were more likely to have recurrence of preterm labor necessitating further tocolytic attempts (P = .048). The patients in the magnesium sulfate group had more adverse side effects, mainly nausea and vomiting (P = .004). There were no differences in birth weight, estimated gestational age at delivery, or neonatal complications between the 2 groups. Conclusions: Oral nicardipine is an effective, safe, and well-tolerated tocolytic agent. In this prospective clinical trial patients randomly assigned to receive oral nicardipine had arrest of preterm labor more rapidly than did those randomly assigned to receive parenteral magnesium sulfate. Patients who received magnesium sulfate were more likely to have adverse medication effects and recurrent preterm labor. (Am J Obstet Gynecol 1999;181:1432-7.)

Pre-PTCA detection of chronic but reversible postischemic myocardial dysfunction by nicardipine.

The aim of the study was to find out whether in patients (n = 24) with one-vessel coronary artery disease, reversibility of related left ventricular (LV) wall motion abnormalities after successful percutaneous transluminal coronary angioplasty (PTCA) can be predicted by the immediate effect of calcium antagonist nicardipine. Dynamic quantitative left cineventriculography performed four times successively (as the control, 30 minutes after oral nicardipine, 10 minutes after PTCA, and 6 months after PTCA) and hemiaxis method (mean relative hemiaxis shortening or Xdeltar%) were used for wall motion analysis of 48 poststenotic LV myocardial segments divided into three groups: hypokinetic noninfarcted (PNHS, n = 25), infarcted (PIS, n = 12), and normokinetic noninfarcted (PNNS, n = 11) and of 24 normal LV myocardial segments (NS). In PNHS and PIS close correlation (r = 0.75, P < 0.0001 and r = 0.71, P < 0.005) was demonstrated between postnicardipine improvement (21 +/- 4% to 37 +/- 9%, P < 0.0001, and 16 +/- 7% to 20 +/- 8%, P < 0.0005) and 6 months after PTCA improvement (21 +/- 4% to 33 +/- 7%, P < 0.0001, and 16 +/- 7% to 19 +/- 9%, P < 0.0005) of wall motion. It was loose in PNNS and absent in all three groups immediately after PTCA. The sensitivity of the nicardipine test for 6 months after PTCA reversible LV segmental hypokinesia was high in PNHS (95%) and lower in PIS and PNNS (67% and 60%, respectively). The specificity was 100% in PIS, lower in PNNS (67%), and absent in PNHS (owing to lack of true nonresponders). Immediately after PTCA, contraction significantly improved only in PNHS; the nicardipine test was 100% sensitive but nonspecific. Significant improvement of contraction of all groups of poststenotic LV wall segments is expected 6 months after successful PTCA of related artery stenosis, being well predictable by the pre-PTCA effect of nicardipine, at least in PNHS and in PIS. Immediately after PTCA, only in PNHS can significant improvement of contraction be expected.

Nicardipine as antihypertensive therapy in liver transplant recipients: Results of long-term use

Arterial hypertension is frequent in liver transplant recipients on cyclosporine A (CsA). Nicardipine is a calcium channel blocker (CCB) that has been shown to be efficient in controlling postoperative hypertension. However, its use has been limited in organ recipients because of its reported interaction with CsA metabolism. In this report, we studied the results of the long-term use of nicardipine after liver transplantation. Forty-nine consecutive liver transplant recipients with a follow-up longer than 2 years were studied. Immunosuppressive regimen was based on CsA and prednisone. Patients with immediate postoperative hypertension received intravenous nicardipine, secondarily switched to oral nicardipine (group 1, n = 27). Patients with delayed hypertension (i.e., >2 weeks posttransplant) received other antihypertensive drugs which did not interact with CsA metabolism. These patients and those without hypertension formed group 2 (n = 22). The two groups were similar for age, sex, body weight, and transplantation indications. Interaction of nicardipine with CsA metabolism was confirmed. Whereas cyclosporine blood levels were similar in both groups at any time during the study, the mean cyclosporine daily dose required to achieve such levels was 30% lower in group 1 compared with group 2 (P < .01). This resulted in a significant cost-containment. The use of nicardipine was not associated with an increased incidence of graft rejection or CsA toxicity episodes. The results in liver transplant recipients showed that nicardipine interacts with CsA metabolism, leading to a 30% reduction in CsA dose and does not increase the risk of CsA toxicity or graft rejection. Nicardipine can be used safely for the treatment of arterial hypertension after liver transplantation with a potential cost-containment.(Hepatology 1997 Feb;25(2):430-3)

Nicardipine as antihypertensive therapy in liver transplant recipients: results of long-term use.

Arterial hypertension is frequent in liver transplant recipients on cyclosporine A (CsA). Nicardipine is a calcium channel blocker (CCB) that has been shown to be efficient in controlling postoperative hypertension. However, its use has been limited in organ recipients because of its reported interaction with CsA metabolism. In this report, we studied the results of the long-term use of nicardipine after liver transplantation. Forty-nine consecutive liver transplant recipients with a follow-up longer than 2 years were studied. Immunosuppressive regimen was based on CsA and prednisone. Patients with immediate postoperative hypertension received intravenous nicardipine, secondarily switched to oral nicardipine (group 1, n = 27). Patients with delayed hypertension (i.e., >2 weeks posttransplant) received other antihypertensive drugs which did not interact with CsA metabolism. These patients and those without hypertension formed group 2 (n = 22). The two groups were similar for age, sex, body weight, and transplantation indications. Interaction of nicardipine with CsA metabolism was confirmed. Whereas cyclosporine blood levels were similar in both groups at any time during the study, the mean cyclosporine daily dose required to achieve such levels was 30% lower in group 1 compared with group 2 (P < .01). This resulted in a significant cost-containment. The use of nicardipine was not associated with an increased incidence of graft rejection or CsA toxicity episodes. The results in liver transplant recipients showed that nicardipine interacts with CsA metabolism, leading to a 30% reduction in CsA dose and does not increase the risk of CsA toxicity or graft rejection. Nicardipine can be used safely for the treatment of arterial hypertension after liver transplantation with a potential cost-containment.

Evaluation of the efficacy and safety of oral nicardipine in treatment of urgent hypertension: A multicenter, randomized, double-blind, parallel, placebo-controlled clinical trial: G.B. Habib, L.M. Dunbar, R. Rodrigues, A.C. Neale, K.J. Friday. Section of Cardiology, Veterans Affairs Medical Center, Houston, TX. Am Heart J 1995;129:917–23

Evaluation of the efficacy and safety of oral nicardipine in treatment of urgent hypertension: A multicenter, randomized, double-blind, parallel, placebo-controlled clinical trial: G.B. Habib, L.M. Dunbar, R. Rodrigues, A.C. Neale, K.J. Friday. Section of Cardiology, Veterans Affairs Medical Center, Houston, TX. Am Heart J 1995;129:917–23

Evaluation of the efficacy and safety of oral nicardipine in treatment of urgent hypertension: A multicenter, randomized, double-blind, parallel, placebo-controlled clinical trial

This study was a prospective, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the safety and efficacy of oral nicardipine for the treatment of urgent hypertension in the emergency department. Of 57 patients with urgent hypertension 53 patients were enrolled: 36 men and 17 women, 43 black and 10 white, age range 48 ± 11 years, and diastolic blood pressure 128 ± 7 mm Hg. Patients were randomly assigned to receive 30 mg nicardipine or placebo in blind fashion followed by 30 mg open-label nicardipine in nonresponders. Responders to one or two doses of nicardipine received 30 or 40 mg nicardipine three times a day for 1 week after discharge from the emergency department. Adequate blood pressure reduction, defined as a reduction of diastolic blood pressure to less than 100 mm Hg or by at least 20 mm Hg, was achieved in 65% and 22% of patients who received 30 mg nicardipine or placebo ( p = 0.002). Adequate blood pressure reduction after administration of open-label nicardipine occurred in 76% of the nonresponders to placebo. Blood pressure reductions were maintained at 1 week after discharge. The drug was well tolerated, and no significant adverse events occurred. We conclude that oral nicardipine is a safe and effective drug for the initial treatment of urgent hypertension.

The Effects of Oral Nicardipine on Cardiovascular Response to Tracheal Intubation

The Effects of Oral Nicardipine on Cardiovascular Response to Tracheal Intubation

Influences of the calcium antagonists nicardipine and nifedipine, and the calcium agonist BAY-K-8644, on the pharmacokinetics of propranolol in rats.

To determine the effect of dihydropyridines on the metabolism of propranolol, we studied the effects of a single oral dose of nicardipine, nifedipine, and BAY-K-8644 on the pharmacokinetics of propranolol in male Wistar rats fitted with a catheter in the jugularis vein. Oral propranolol (15 mg/kg and 1.5 mg/kg) and intravenous propranolol (1.5 mg/kg) were administered either alone or together with oral nicardipine (2.5 mg/kg). Oral propranolol (15 mg/kg) was administered with oral nifedipine (1.5 mg/kg) and with oral BAY-K-8644 (1.5 mg/kg). Nicardipine increased significantly the AUC and Cmax of oral propranolol (1.5 mg/kg and 15 mg/kg). However, the plasma concentration time curve of intravenous propranolol (1.5 mg/kg) was unaffected. Nifedipine also significantly increased the AUC and Cmax of oral propranolol (15 mg/kg), whereas with BAY-K-8644 there was only a slight increase in the bioavailability of oral propranolol (15 mg/kg). The results indicate that the dihydropyridine calcium antagonists decrease the metabolism of propranolol as a result of a decrease in first-pass clearance. Although an interaction at the level of cytochrome P450 may also be involved, the results of the present study suggest that the inhibitory effect can be largely attributed to changes in liver blood flow.

Evaluation of lipid metabolism during antihypertensive treatment with nicardipine sr.

The antihypertensive and metabolic effects of oral nicardipine SR 40 mg b.i.d. have been studied in 18 (15 m, 3 f; age 52.7 y) hypertensives with mild hypercholesterolaemia, treated for 3 months after a 2 week period on placebo. An iv Fat Tolerance Test (FTT) was also performed in 8 patients following placebo, treatment with acute nicardipine 20 mg and chronic administration of nicardipine SR. There was a significant fall in BP from 160/97 on placebo to 147/87 after 3 months on nicardipine SR with no change in heart rate. Blood lipids did not change significantly. The disappearance rate of the lipid emulsion in the ivFTT showed no significant change (K2 was 1.93%/min after placebo, 1.84 after nicardipine 20 mg and 1.71 after chronic treatment). The results suggest that nicardipine is an effective antihypertensive drug and that it is devoid of untoward effects on lipid metabolism.

Nicardipine in the prevention of spasm-induced neurological deficits after subarachnoid hemorrhage: A dose-ranging study

The tolerability of four doses of intravenous nicardipine (0.03, 0.08, 0.11, and 0.15 mg/kg/h) was assessed in this randomized multicenter, parallel-group study. Fifty-two patients with Hunt and Hess grade I-III aneurysmal subarachnoid hemorrhage were treated with intravenous nicardipine beginning within 4 days of bleeding, for a mean duration of 12.6 days; this treatment was followed by administration of oral nicardipine 90–120 mg until day 30. Hypotension was the main side effect, and it occurred only in the two groups that received the highest doses. However, it was possible to continue nicardipine in all cases at lower doses or even without modification, and hypotension was never responsible for any deleterious clinical effect.

Response of the pulmonary circulation to acetylcholine, calcitonin gene-related peptide, substance P and oral nicardipine in patients with primary pulmonary hypertension

Endothelium-dependent vasodilation of the pulmonary vascular bed was investigated in five patients with primary pulmonary hypertension. Three endothelium-dependent vasodilators (acetylcholine, calcitonin gene-related peptide and substance P [in two patients]) were infused sequentially into the right atrium, followed by nicardipine given orally during full hemodynamic monitoring.Acetylcholine, calcitonin gene related peptide and substance P had no effect on pulmonary artery pressure, total pulmonary vascular resistance or cardiac output, although calcitonin gene-related peptide significantly decreased systemic arterial systolic pressure from 132 ± 34 to 113 ± 33 mm Hg. In contrast, oral nicardipine decreased total pulmonary vascular resistance from 23 ± 12 to 13 ± 8 U, with a concomitant increase in cardiac output from 3.1 ± 1 to 4.7 +- 2 liters · min−1and decrease in systemic vascular resistance from 30 ± 9 to 13 ± 4 U.Thus, despite the presence of a reversible component in these five patients with primary pulmonary hypertension, pulmonary vascular resistance did not decrease ia response to the infused endothelium-dependent vasodilator agents, indicating that endothelium-dependent vasodilation is impaired ia these patients.