Effects Of Urapidil Research Articles

Clinical Effect of Urapidil and Nitroglycerin in Pre-Hospital Care for Hypertensive Emergency

Clinical Effect of Urapidil and Nitroglycerin in Pre-Hospital Care for Hypertensive Emergency

Investigation of the Curative Effect of Urapidil on Intestinal Inflammation and Oxidative Damage: An Experimental Study

Investigation of the Curative Effect of Urapidil on Intestinal Inflammation and Oxidative Damage: An Experimental Study

The effect of urapidil, an alpha-1 adrenoceptor antagonist and a 5-HT1A agonist, on the vascular tone of the porcine coronary and pulmonary arteries, the rat aorta and the human pulmonary artery

Urapidil (Eupressyl®) an antihypertensive drug acting as an α1 antagonist and a 5-HT1A agonist, may be of special interest in the treatment of hypertension associated with preeclamptic toxaemia and hypoxia-induced pulmonary arterial vasoconstriction. However, the effect of urapidil on vascular tone has been poorly investigated. Vascular reactivity was evaluated using pulmonary and coronary arteries from 36 pigs, aortae from 22 rats and 9 human pulmonary artery samples suspended in organ chambers. Concentration-relaxation curves either to urapidil, 5-HT, or the 5-HT1A receptor agonist 8-OH-DPAT were constructed after pre-contraction of rings. Pig pulmonary and coronary artery rings were contracted with U46619, a thromboxane mimetic, rat aortic rings with either endothelin-1 or phenylephrine, and human pulmonary artery rings with U46619 or phenylephrine. Urapidil markedly inhibited phenylephrine-induced contractions in rat aortic rings with and without endothelium with a more pronounced effect observed in rings without endothelium. Both 5-HT and 8-OH-DPAT failed to induce relaxation in rat aortic rings with an intact endothelium. 5-HT, but not urapidil and 8-OH-DPAT, induced a concentration-dependent relaxation in the porcine coronary and pulmonary artery rings with an intact endothelium (P<0.05). 5-HT and phenylephrine but not urapidil caused concentration-dependent contractions in human pulmonary artery rings. The present findings, while confirming that urapidil is a potent inhibitor of α1-adrenoceptor-induced contraction, do not support the role of 5-HT1A receptor activation in the control of the vascular tone of the different types of arteries tested in response to urapidil. In addition, they indicate that urapidil seems to preferentially target arteries with endothelial dysfunction.

COMBINED ACTION ANTIHYPERTENSIVE AGENT URAPIDIL: EFFECTIVENESS AND SAFETY IN CLINICAL PRACTICE

The paper reviews the clinical practice potential of a combined action antihypertensive medication urapidil for the treatment of patients with acute elevation of blood pressure (BP) and confirms urapidil effectiveness and good tolerability. Urapidil action mechanisms, pharmacodynamics, and pharmacokinetics are discussed, together with the results of the key clinical trials which have demonstrated antihypertensive effectiveness and safety of this agent. Additional beneficial effects of urapidil, such as reduction of the increased pulmonary artery BP and improvement of bronchial conductivity, are also described.

Pulmonary Gas Embolism as a Potential Cause of Hypoxia Immediately After Cardiopulmonary Bypass

THE DEVELOPMENT OF HYPOXIA is not uncommon during cardiac surgery. 1 Yende S. Wunderink R. Causes of prolonged mechanical ventilation after coronary artery bypass surgery. Chest. 2002; 122: 245-252 Crossref PubMed Scopus (50) Google Scholar Causes of hypoxia include cardiogenic and/or noncardiogenic pulmonary edema, atelectasis, pneumonia, surgical trauma of pulmonary vasculatures, and increased ventilation-perfusion (VA/Q) mismatch from vasodilators. 1 Yende S. Wunderink R. Causes of prolonged mechanical ventilation after coronary artery bypass surgery. Chest. 2002; 122: 245-252 Crossref PubMed Scopus (50) Google Scholar , 2 Wan S. LeClerc J.L. Vincent J.L. Inflammatory response to cardiopulmonary bypass. Chest. 1997; 112: 676-692 Crossref PubMed Scopus (776) Google Scholar , 3 Gale G.D. Teasdale S.J. Saunders D.E. et al. Pulmonary atelectasis and other respiratory complications after cardiopulmonary bypass and investigation of aetiological factors. Can Anaesth Soc J. 1979; 26: 15-21 Crossref PubMed Scopus (62) Google Scholar , 4 Möllhoff T. Van Aken H. Mulier J.P. et al. Effects of urapidil, ketanserin and sodium nitroprusside on venous admixture and arterial oxygenation following coronary artery bypass grafting. Br J Anaesth. 1990; 64: 493-497 Crossref PubMed Scopus (20) Google Scholar , 5 Franke A. Lante W. Fackeldey V. et al. Pro-inflammatory cytokines after different kinds of cardiothoracic surgical procedures: Is what we see what we know?. Eur J Cardiothorac Surg. 2005; 28: 569-575 Crossref PubMed Scopus (144) Google Scholar , 6 Prondzinsky R. Knüpfer A. Loppnow H. et al. Surgical trauma affects the pro-inflammatory status after cardiac surgery to a higher degree than cardiopulmonary bypass. J Thorac Cardiovasc Surg. 2005; 129: 760-766 Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar , 7 Spies B.D. Transfusion of blood products affects outcome in cardiac surgery. Semin Cardiothorac Vasc Anesth. 2004; 8: 267-281 Crossref PubMed Scopus (120) Google Scholar , 8 Bux J. Transfusion-related acute lung injury (TRALI): A serious adverse event of blood transfusion. Vox Sang. 2005; 89: 1-10 Crossref PubMed Scopus (191) Google Scholar Pulmonary gas embolism (PGE) by air or medical gases potentially can occur in cardiac surgery involving opening of the right heart because it is impossible to remove all traces of air from the cardiac chambers before closing the heart. 9 Lumb A.B. Pulmonary vascular disease. in: “Nunn’s” Applied Respiratory Physiology Sixth Edition. Elsevier, Philadelphia, Pennsylvania2005: 387-398 Google Scholar However, PGE has not been mentioned often as a cause of hypoxia during cardiac surgery. An adult patient who underwent corrective surgery for incomplete endocardial cushion defect (ECD) and developed severe hypoxia immediately after cardiopulmonary bypass (CPB), in which case the authors hypothesized PGE as a possible cause, is presented.

Effect of urapidil on rat brain catecholamine synthesis.

The effects of urapidil, a clinically effective antihypertensive drug, on the in-vivo rate of synthesis of rat brain noradrenaline (NA) and dopamine (DA) was determined. A significant dose-dependent increase in dopa concentration by urapidil after dopa decarboxylase inhibition by NSD 1015 was observed in brain stem (3-30 mg kg-1 i.p.) and striatum (10-30 mg kg-1 i.p.), indicating increased NA and DA turnover, respectively, most probably a result of central blockade of brainstem alpha 1-adrenergic and striatal DA receptors. These results indicate that urapidil may possibly exert its central hypotensive action in part by a reduced influence on brain stem NA, thus reducing central sympathetic outflow.

Effects of Urapidil on Catecholamine Turnover and Release in the Central Nervous System of the Rat

The actions of urapidil, prazosin, idazoxan, and haloperidol on the turnover of noradrenaline in the hypothalamus and dopamine in the nucleus accumbens of the rat were investigated using changes in the ratios of 3-methoxy-4-hydroxyphenyl-glycol/noradrenaline (MHPG/NA) and 3,4-dihydroxyphenylacetic acid/dopamine (DOPAC/DA), respectively, as measures for drug-induced effects. Urapidil (2.5-30 mg kg-1 i.v.) increased the ratios of MHPG/NA and DOPAC/DA. Its effects on NA turnover were maximal at 60 min (160% of control at 30 mg kg-1), and on DA turnover at 30 min (138% of control at 30 mg kg-1). Prazosin (0.5-2.5 mg kg-1 i.v.) had no effect, but the high dose of 5 mg kg-1 i.v. significantly increased the ratio of MHPG/NA in the hypothalamus. Idazoxan (2-50 mg kg-1 i.v.) and haloperidol (0.02-0.5 mg kg-1 i.v.) selectively enhanced turnover of NA and DA, respectively. In experiments on field-stimulated overflow of tritium from slices of hypothalamus and nucleus accumbens labelled with [3H]NA or [3H]DA, respectively, urapidil (1 mumol L-1) facilitated the evoked responses in both regions. Prazosin (0.1 mumol L-1) had no effect in either of the two areas. Idazoxan (0.1 mumol L-1) increased stimulated overflow of [3H]NA from the hypothalamus but not of [3H]DA from the nucleus accumbens. Conversely, haloperidol (0.1 mumol L-1) greatly enhanced evoked overflow of [3H]DA but not of [3H]NA. From the present results it is concluded that urapidil has an antagonistic effect at central alpha 2-adrenoceptors and also a weak antagonistic action at central dopamine D2-receptors.

Deviating central hypotensive activity of urapidil in the cat.

Urapidil, a novel antihypertensive drug, as well as possessing a peripheral alpha 1-adrenoceptor antagonistic effect, also has a significant degree of central hypotensive activity. When injected into the left vertebral artery of chloralose-anaesthetized cats the dose-dependent hypotensive effect of the drug was much stronger than after its systemic administration. Prior treatment, also via the vertebral artery, with various receptor antagonists (yohimbine, prazosin, diphenhydramine, metiamide, sulpiride, pirenzepine, R 56413, naloxone) did not antagonize the central hypotensive effect of urapidil administered subsequently. Accordingly, the central hypotensive action of urapidil is not mediated by central receptors of the following types: alpha 2- or alpha 1-adrenoceptors; H1- and H2-histamine; dopaminergic; muscarinic; 5-hydroxytryptamine; opiate. As such the mechanism of the central hypotensive action remains unexplained. It obviously deviates from that of classical centrally acting antihypertensive drugs like clonidine, guanfacine and alpha-methyldopa, which are agonists of central alpha 2-adrenoceptors.

Neonatal transient respiratory depression after maternal urapidil infusion for hypertension

Urapidil is a potent antihypertensive drug that has been in clinical use for more than 20 years. It has been proven to be an effective and well-tolerated antihypertensive drug during pregnancy, but clinical experiences with urapidil have been described in only a limited number of studies. There have also been only limited observations on the (side-)effects of urapidil on the neonate. We describe here a case of postnatal transient respiratory depression following maternal administration of urapidil. We suggest that the fetal and neonatal effects of more recently implemented antihypertensive drugs, such as urapidil, should be included in a prospective evaluation of antihypertensive treatment of women during pregnancy. Infants of mothers who received urapidil should be carefully watched in the immediate postnatal phase as urapidil may still exert some significant effects on the neonate.

Rapid determination of subnanogram urapidil using flow injection enhancement chemiluminescence

A sensitive flow-injection (FI) chemiluminescence (CL) for the determination of urapidil is described in this paper. It is based on the enhancement effect of urapidil on the CL reaction between luminol and hydrogen peroxide. The increment of CL intensity is proportional to the concentration of urapidil in the range 0.1−10 ng/mL (R 2=0.9986), with a detection limit (3σ) of 0.03 ng/mL. The whole process, at a flow rate of 2.0 mL/min, including sampling and washing, could be completed in 0.5 min, and the relative standard deviation (RSD) at the concentration of 0.1, 1.0, and 10.0 ng/mL was less than 3.0% (n = 5). The proposed method has been successfully applied for the determination of urapidil in pharmaceutical preparation, human urine, and serum.

Effect of Urapidil on Diabetic Neurogenic Bladder

Effect of Urapidil on Diabetic Neurogenic Bladder

The effect of urapidil and ramipril on hyperglycemia in streptozotocin diabetic rats.

Angiotensin-converting enzyme inhibitors and alpha1-adrenoceptor antagonists improve glucose disposal in diabetes mellitus. We compared the effect of the antihypertensive hybrid drug urapidil [alpha1-adrenoceptor antagonist serotonin 1A (5-hydroxytryptamine 1A, 5-HT1A) receptor agonist] on hyperglycemia in streptozotocin diabetic rats with the angiotensin-converting enzyme inhibitor ramipril. 5-HT1A receptor agonists induce hyperglycemia. This could be an important disadvantage during treatment of diabetes mellitus with urapidil. Diabetes was induced by streptozotocin (70 mg/kg i.p.). Treatment for 7 days (ramipril 10 mg/kg p.o.; urapidil 20 mg/kg p.o.) significantly decreased mean blood glucose values (urapidil: 15.7+/-0.9 mmol/l, P=0.007; ramipril: 15.0+/-0.8 mmol/l, P=0.038 vs. diabetic control group: 18.7+/-1.0 mmol/l). Both drugs reduced significantly blood pressure, urinary glucose, water consumption, and food requirement. Serotonin concentration in the brain (medulla oblongata, pituitary) was not affected. A normalization comparable with healthy control rats was observed only in a diabetic control group with insulin therapy. In conclusion, our results demonstrate that the antihypertensive drug urapidil has no detrimental effect on hyperglycemia compared with the angiotensin-converting enzyme inhibitor ramipril in experimental diabetes mellitus despite its 5-HT1A receptor agonistic properties.

Reduction of cardiovascular response to endotracheal intubation in normotensive patients by urapidil.

Urapidil is an antihypertensive drug with actions of α1-receptor blockade and 5-HT1A (5-hydroxytryptamine) receptor stimulation. Although many agents have been used to attenuate the cardiovascular response to endotracheal intubation, few of them are related to urapidil. This study was done to evaluate the effects of urapidil on reducing the cardiovascular response to intubation. In this randomized, double-blind, placebo-controlled study, 30 ASA I-II adult surgical patients without cardiovascular disease were divided into two groups of 15 each, receiving either an i.v. bolus of 0.6 mg·kg-1 urapidil 5 min before intubation or an equivalent volume of saline as control. The heart rate and the systolic and diastolic blood pressure were determined intermittently for 5 min before and 10 min after intubation. The mean blood pressure, product of systolic blood pressure and heart rate, and coefficient of variation (CV) of these variables around intubation were calculated. Urapidil had no effects on the heart rate (P>0.05), could effectively attenuate the increases in the diastolic and mean arterial pressures (P<0.05) caused by intubation, but had a weak effect on the systolic pressure (P>0.05) and its product with heart rate. In addition, the CV of the diastolic pressure and mean arterial pressure was greater (P<0.05) in the urapidil group than in the control group, which meant that the induction procedure with urapidil was not more stable than that when saline was used as placebo. The effects of urapidil on reducing the cardiovascular response to intubation are mild when uradipil is used 5 min before intubation. As urapidil mainly decreases diastolic blood pressure, an important determinant of cardiac blood supply, and it makes systolic, diastolic, and mean blood pressure fluctuate strongly during induction, we should be alert about its latent detrimental effect on patients, especially those with ischemic heart disease.

The Effect of Urapidil on Neurogenic Bladder

The Effect of Urapidil on Neurogenic Bladder

Comparison of the effects of urapidil and sodium nitroprusside on haemodynamic state, myocardial metabolism and function in patients during coronary artery surgery

We have compared, in an open randomized study, the effects of sodium nitroprusside (SNP) and urapidil on haemodynamic state and myocardial function and metabolism in two groups of patients undergoing elective coronary artery surgery. Sixty patients were allocated randomly to one of two groups: group SNP (n = 29) received SNP at an initial rate of 1-2 micrograms kg-1 min-1; group URA (n = 31) received one or more bolus injections of urapidil 25 mg and an i.v. infusion at an initial rate of 11-21 micrograms kg-1 min-1. Baseline measurements were obtained 10 min after introduction of an echotransducer into the oesophagus. Subsequently, vasodilator therapy was started in both groups. Infusion rates were adjusted to maintain systolic arterial pressure at 80-120% of baseline values (or mean arterial pressure < 100 mm Hg). Additional measurements were obtained 10 min after the start of vasodilator therapy and after sternotomy when the pericardium was opened. At each measuring time a complete haemodynamic profile, coronary sinus blood flow (CSBF) curves, transoesophageal echocardiographic images, and arterial and coronary venous blood samples were obtained. Arterial pressure was controlled adequately in both groups. After sternotomy, heart rate and cardiac index increased in both groups. At that time, there was a significant increase in myocardial oxygen consumption and CSBF in group URA (P < 0.05). However, the ratio between myocardial oxygen demand and oxygen supply remained unchanged and there was no difference in the number of ischaemic episodes between the groups.

The Effects of Urapidil on Changes of Arterial Blood Pressure and Heart Rate to Endotracheal Intubation

The Effects of Urapidil on Changes of Arterial Blood Pressure and Heart Rate to Endotracheal Intubation

Effects of Urapidil on Coronary Blood Flow During Graded Treadmill Exercise

We examined the effects of the alpha-adrenergic blocking agent urapidil on coronary blood flow (CBF) and myocardial O2 consumption during exercise in 11 dogs trained to run on a motor-driven treadmill. Left circumflex coronary artery (LCX) BF was measured with an electromagnetic flowmeter, and aortic and coronary sinus electromagnetic flowmeter, and aortic and coronary sinus catheters allowed determination of myocardial arteriovenous O2 extraction. During control conditions, graded treadmill exercise caused progressive increases in myocardial O2 consumption, which resulted from regular increases in CBF as well as increased O2 extraction by myocardium. Urapidil 3 mg/kg blocked the response to the selective alpha 1-adrenergic agonist phenylephrine (PE 5 micrograms/kg intravenously, i.v.), and significantly decreased arterial blood pressure (BP) at rest and during exercise. Heart rate (HR) was significantly faster than control during the lightest level of exercise after urapidil. Similarly, CBF was significantly increased during light and moderate exercise after urapidil administration. Urapidil caused a slight decrease in myocardial O2 extraction, with an increase in coronary sinus O2 tension. These data indicate that urapidil antagonized adrenergic coronary vasoconstriction, which acted to limit the increase in CBF that occurred during exercise.

Effect of urapidil on the action potentials in the guinea-pig ventricular myocardium

The electrophysiological effects of urapidil, a new alpha 1-adrenoceptor antagonist, were assessed in the reserpinized guinea-pig ventricular myocardium. Urapidil suppressed the maximal rate of rise (Vmax) of steady-state action potentials elicited by the fast responses at high concentrations independently of blockade of myocardial alpha-adrenoceptors, but not the Vmax of Ca(2+)-dependent slow action potentials of partially depolarized muscles in concentrations tested (up to 1.1 mM). Urapidil at high concentrations prolonged the action potential durations of the fast and slow responses in a manner similar to the quinidine-like antiarrhythmic drugs. These results suggest that the inhibitory effect of urapidil on the slow inward Ca2+ current and the Na+ current is in practice negligible.

The effect of urapidil on responses to phenylephrine, angiotensin and isoprenaline in man

Intravenous urapidil, 40 mg bolus followed by an infusion of 18 mg.h-1 for 2 h was administered to 6 female non-patient volunteers. Randomised cumulative dose response curves to angiotensin, phenylephrine and isoprenaline were performed before and commencing 30 min after the start of the infusion of urapidil. Urapidil significantly reduced supine systolic blood pressure, 118.5 mm Hg to 105.3. The diastolic blood pressure was not significantly reduced, heart rate was not affected. Urapidil did not affect the responses to angiotensin or isoprenaline. Urapidil inhibited the pressor response to phenylephrine. The dose required to increase systolic blood pressure by 20 mm Hg increased from 156.9 micrograms.min-1 before to 685 micrograms.min-1 during urapidil; Dose ratio from individual values of 4.58. Urapidil concentrations were not significantly different before and after each agonist infusion. It is concluded that urapidil has alpha 1-adrenoceptor blocking activity in man without any non specific vasodilator action and that it is devoid of beta adrenoceptor blocking action.

Effect of urapidil on the performance of ischemic myocardium in anesthetized dogs

Urapidil (URA) is used to treat acute hypertension in patients with coronary artery disease, but the effect of URA on the performance of ischemic myocardium has not yet been investigated. The present study was intended to assess the function of ischemic myocardium following URA administration. In eight anesthetized (piritramide) open-chest dogs systolic contraction (dL) and end-diastolic length (edL) of myocardium supplied by the left descending (LAD) and circumflex (LCA) coronary arteries were measured by sonomicrometry simultaneously with aortic pressure (AoP), left ventricular end-diastolic pressure (LVedP), heart rate (HR), stroke volume (SV), and LAD-flow (QLAD). QLAD was reduced by LAD stenosis to about 50% of control, decreasing dLLAD by 55%. Concomitantly, edLLAD increased by about 9% and LVedP by 22%, whereas AoP decreased by 5%. Then, URA was given i.v. (0.25 + 0.25 + 0.50 + 1.0 mg/kg) in 15-min intervals. Following URA, the performance of the non-ischemic area was not systematically affected, but dLLAD increased by about 50%. This could neither be related to the significant reduction in afterload (AoP: -8%), nor to an increase in preload (LVedP and edLLAD did not change significantly), nor to an improved oxygen supply via the LAD (QLAD even decreased), although an increased collateral flow the LCA could not be excluded. The increase in systolic shortening correlated very closely to a decrease in heart rate (r = -0.92). It is concluded that the improved function of ischemic myocardium following urapidil resulted from a reduced oxygen demand in consequence to the decrease in heart rate.