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Efficacy of angiotensin II antagonists in treatment of essential hypertension associated with ischemic heart disease
130A
POSTERS: Antihypertensive Drugs
AJH–May 2003–VOL. 16, NO. 5, PART 2
P-255 EFFECTS OF A FIXED-DOSE ACE INHIBITORDIURETIC COMBINATION ON AMBULATORY BLOOD PRESSURE AND ARTERIAL PROPERTIES IN ISOLATED SYSTOLIC HYPERTENSION: COMPARISON WITH CALCIUM CHANNEL BLOCKER AND DIURETIC THERAPY Joanne M Ferguson, Jack Minas, Siky Siapantas, Paul A Komesaroff, Krishnankutty Sudhir. Hormones and Vasculature Laboratory, Baker Medical Research Institute, Melbourne, VIC, Australia; Center for Cardiovascular Interventions, Stanford University, Palo Alto, CA. The ideal therapy for patients with isolated systolic hypertension (ISH) is unclear; diuretics, calcium channel blockers (CCB’s) and ACE inhibitors are all used in clinical practice. Ambulatory blood pressures (ABP) are superior to clinic BP in ISH as predictors of cardiovascular risk. ISH is characterized by increased arterial stiffness, also a predictor of cardiovascular events. We hypothesized that a fixed-dose ACE-inhibitor/diuretic combination would reduce ABP and arterial stiffness in ISH more than monotherapies. Using a double-blind, randomized, cross-over design, the effects of 8 wks of Fosinopril/Hydrochlorothiazide combination (FOS-HCT, 10/12.5mg, titrated up to 20/12.5mg) were compared with CCB (AMLO, Amlodipine, 5mg titrated up to 10mg) and diuretic (INDA, Indapamide, 2.5mg) monotherapy in 28 patients with ISH (mean BP 165/86⫾2/1). Each patient received all 3 therapies with a 2 wk washout period in between; treatment order was randomly selected. Effects of therapy were assessed on 24h ABP, clinic BP, and applanation tonometry-derived augmentation index, a measure of wave reflection and an indirect marker of vascular stiffness. At 8 wks, the fall in average 24h systolic BP (SBP) and night-time SBP were greater in the FOS-HCT group, compared to AMLO and INDA (Table). The decrease in augmentation index was also greater in the FOS-HCT group, compared to AMLO (Table). There was no difference between therapies in their effects on clinic systolic (p⫽0.23) or diastolic BP (p⫽0.22), a.m. measurements made 2-3 hrs after dosing of antihypertensive therapy, nor on diastolic ABP, (24h, diurnal or nocturnal). Thus, compared with either CCB or diuretic therapy a fixed-dose ACE-inhibitor/diuretic combination induces greater reductions in systolic ABP, particularly at night, favorable effects that may be related to a decrease in the intensity of, or delay in, arterial wave reflections. ACE-inhibitor/diuretic combination therapy is thus a useful approach to cardiovascular risk reduction in ISH. Reduction in 24h, Day, and Night Systolic ABP (mmHg) and Augmentation Index (%) Variable
FOS/HCT
AMLO
INDA
P Value
⌬24h SysABP ⌬Day SysABP ⌬Night SysABP ⌬Aug. Index
17 ⫾ 2 16 ⫾ 2 18 ⫾ 2 10.3 ⫾ 1.9
14 ⫾ 1 15 ⫾ 2 13 ⫾ 2 3.6 ⫾ 2.1
12 ⫾ 1 13 ⫾ 2 12 ⫾ 2 6.6 ⫾ 1.4
0.005 0.432 0.021 0.035
Key Words: isolated systolic hypertension, ACE inhibitors, Diuretics
P-256 L- PLUS N- TYPE CA2ⴙ CHANNEL BLOCKER CILNIDIPINE REDUCED ARRHYTHMOGENIC SUBSTRATES IN THE CANINE SUDDEN CARDIAC DEATH MODEL WITH HYPERTENSION Akira Takahara, Atsushi Sugiyama, Yoshioki Satoh, Yuji Nakamura, Tomoyuki Konda, Keitaro Hashimoto. Pharmaceutical Research Laboratories, Pharmaceuticals Company, Ajinomoto Co., Inc, Kawasaki, Kanagawa, Japan; Department of Pharmacology, University of Yamanashi Faculty of Medicine, Tamaho, Yamanashi, Japan. The chronic atrio-ventricular (AV) conduction block dog has been used as a sudden cardiac death model complicating systemic hypertension, of which arrhythmogenic substrates can be potentiated by both endogenous neurohumoral factors like epinephrine and drugs such as IKr inhibitors. In
this study, we assessed the effects of a vascular L- and sympathetic N-type Ca2⫹ channel blocker cilnidipine on hemodynamic, electrophysiological and neurohumoral parameters in this model to estimate its new clinical application. Cilnidipine in a dose of 5mg/day was orally administered to the AV block dogs for 4 weeks. Holter ECG, cardiohemodynamic variables and the monophasic action potential (MAP) duration were measured before and 4 weeks after the start of drug administration (n⫽7). Cilnidipine decreased the mean blood pressures from 144⫾6 to 118⫾10 mmHg. Also, cilnidipine increased the cardiac output from 1.7⫾0.1 to 2.4⫾0.3 l/min, decreased the plasma epinephrine concentration from 305⫾43 to 201⫾40 pg/ml, shortened MAP duration from 270⫾16 to 233⫾12 msec, and decreased the number of premature ventricular contractions from 284⫾177 to 25⫾16 beats/21 hr. These results suggest that cilnidipine decreased the blood pressure, reduced plasma epinephrine level and promoted the ventricular repolarization process of the AV block dogs, which would be possibly exerted through both L- and N-type Ca2⫹ channel inhibitions. Thus, 4 weeks administration of cilnidipine can reduce the arrhythmogenic substrates of the canine sudden cardiac death model. Key Words: calcium channel blocker, arrhythmia
P-257 LEVAMLODIPINE THERAPY FOR HYPERTENSION AFTER KIDNEY TRANSPLANTATION S. D. Tang, J. Qi, Z. W. Han, Z. L. Ming. Shanghai Institute of Hypertension, Rui jin Hospital, Shanghai, P.R., China. Hypertension after kidney transplantation in a special type of secondary hypertension which is a risk factor for the development of complications of hypertension such as renal failure. Apart from control of blood pressure, levamlodipine (levogyral Amlodipine), a long-acting calcium blocker has been shown to protect renal function, 20 cases (M:15,F:5, age 43⫾11.3 years. Range 22-60) were been randomly selected from kidney transplantation patients, all previous antihypertension medication was discontinued before the start of the study. A baseline sitting diastolic blood pressure of ⱖ95mmHg and ⱕ114mmHg and systolic blood pressure of ⱕ190mmHg at the end of dismedication were taken as criteria for study entry. The duration of active treatment with levamlodipine was two months. The initial dose give was 2.5mg levamlodipine as a once-daily dose, after one month of treatment with 2.5mg levamlodipine, patients not responding to this dose regimen received 5mg as a once-daily dose for a further one month treatment. Responders to 2.5mg Levamlodipine continued to take the same dose until the end of the study, after two months of active treatment, SBP, DBP, blood nitrogen decrease obviously (P⬍0.01, ⬍0.01, ⬍0.01, ⬍0.05), while the serum creatine and the blood cyclosporin concentration are not increase (P⬎0.05), without affecting to blood lipids, serum K⫹, serum Na⫹, serum C1-, serum uric acid. Monotherapy with levamlodipine in a dose range of 2.5-5mg oncedaily achieved normalization of blood pressure in 85% hypertension patients after kidney transplantation, at the same time, renal function were improved. Key Words: Levamlodipine, Kidney, Transplantation
P-258 EFFICACY OF ANGIOTENSIN II ANTAGONISTS IN TREATMENT OF ESSENTIAL HYPERTENSION ASSOCIATED WITH ISCHEMIC HEART DISEASE Victor K. Tashchuk, Tatiana O. Kulik. Dept.of Cardiology, Bukovinian State Medical Academy, Chernivtsy, Chernivtsy District, Ukraine; Dept.of Cardiology, Bukovinian State Medical Academy, Chernivtsy, Chernivtsy District, Ukraine. The aim of the investigation was to study the effect of irbesartan (a highly selective angiotensin II antagonist) and its influence on coronary reserve
AJH–May 2003–VOL. 16, NO. 5, PART 2
and functional state of myocardium in patients with essential hypertension in combination with stable angina pectoris. Stress-echocardiography (EchoCG) under the conditions of transesophageal electrocardiostimulation (TEES) was performed and 24-hour Holter ECG monitoring (HM) was recorded in 172 patients (98 men, mean age 52.2⫾1.8 years) before and after 4 week treatment period with irbesartan (80 mg/day orally). Under the irbesartan action the frequency of the cessation of TEES increased from 138.4⫾2.2 to 149.6⫾1.4 imp/min (p⬍0.001), while the summary ST-segment depression decreased from 4.86⫾0.22 to 3.12⫾0.13 mm (p⬍0.001). The results of EchoCG have testified the increase of ejection fraction (EF) at rest from 50.1⫾0.7 to 58.5⫾0.8 % (p⬍0.001). The decrease of EF at peak of TEES was -10.5 % at the beginning and -3.2 % at the end of irbesartan treatment period. According to the data of HM, irbesartan significantly reduced the frequency (from 2,1⫾0.3 to 1,3⫾0.1 episodes, p⬍0.01) and the total duration of painful ischemic episodes (from 37.3⫾5.5 to 20.5⫾4.6 minutes, p⬍0.02). The same tend was registered for silent ischemic episodes: the frequency decreased from 3,3⫾0.5 to 2,5⫾0.4 episodes (p⬎0.2) and total duration from 51.7⫾6.4 to 42.1⫾4.8 minutes (p⬎0.2). Thus, the results show that irbesartan treatment has positive effect on coronary reserve and improves myocardial contractility in patients with essential hypertension associated with ischemic heart disease. Key Words: essential hypertension, irbesartan, ischemic heart disease
P-259 AMLODIPINE: INFLUENCE ON REGIONAL MYOCARDIAL CONTRACTILITY Victor K. Tashchuk, Pavlo R. Ivanchuk, Ivanna A. Tashchuk. Dept. of Cardiology, Bukovinian State Medical Academy, Chernivtsy, Chernivtsy District, Ukraine; Dept. of Cardiology, Bukovinian State Medical Academy, Chernivtsy, Chernivtsy District, Ukraine; Dept. of Cardiology, Bukovinian State Medical Academy, Chernivtsy, Chernivtsy District, Ukraine. In order to determinate the efficiency of amlodipine’s (Pfizer) influence on the capability of the left ventricular (LV) myocardial contractility, 40 patients with essential hypertension and ischemic heart disease (stable angina pectoris) were examined after the dynamic contractility of the left ventricle myocardium was tested. Patients were examined during the acute period of the amlodipine test and under the background of 10 days of treatment. Clinical effect of amlodipine is related to the blood pressure stabilization. In average on 3rd day of treatment, amlodipine lead to systolic blood pressure decrease up to 24,7% (p⬍0.05) and diastolic blood pressure decrease up to 24,2% (p⬍0.05). Bicycle ergometry was carried out until clinical and diagnostic criteria were reached, the test was stopped when 92,2% out of the calculated sub maximum load was carried out. Echocardiography at that point failed to show any substantial dynamics of the volume indexes and the general ejection fraction (GEF). On the other hand analyses of the regional ejection fraction (REF) testify, that the use of amlodipine, already during the acute period of testing, lead to it’s improvement, the changes were authentic for REF8 (p⬍0.05), in other regions of the left ventricle, increase myocardial contractility tendencies were noted. Initial parameters of the regional contractility in terms of the 10 days amlodipine treatment, regional contractility profile changing tendencies was characterized with decrease for the REF3-5 and increase of the REF1-2, REF6-12, changes for REF1 were authentic (p⬍0.05). At the height of the recurring amlodipine test, compared to the initial amlodipine test, similar change tendencies were registered along with the increase of the initial REF1-2 and REF6-12 in view of REF3-5 decrease. Thus, it is defined that amlodipine, even in a short treatment term, possesses positive influence on the regional contractility. Key Words: essential hypertension, amlodipine, regional contractility
POSTERS: Antihypertensive Drugs
131A
P-260 ANTAGONISTS OF ANGIOTENSINE RECEPTORS AND ACUTE STRESS-TEST : POSSIBILITY IN TREATMENT OF HYPERTENSION Victor K. Tashchuk, Svetlana I. Grechko. Dept. of Cardiology, Bukovinian State Medical Academy, Chernivtsy, Chernivtsy District, Ukraine; Dept. of Cardiology, Bukovinian State Medical Academy, Chernivtsy, Chernivtsy District, Ukraine. 46 patients who had essential hypertension on background concomitant ischemic heart disease were examined with the aim of study the antiischemic effect of antagonists of angiotensine II (AT1) receptors (irbesartan, valsartan and eprosartan), using pair stress-test – transoesophageal electrocardiostimulation (TEES). The frequency of TEES cessation increased using valsartan (130.1⫾1.5 to 135.3⫾2.1 imp/min, ⫹4,0%, p⬍0.05), insignificantly in case of irbesartan usage (135.4⫾2.4 to 140.6⫾1.8 imp/min, 3,9%, p⬎0.05) and eprosartan (127.6⫾1.8 to 131.5⫾1.4 imp/min, 3,1%, p⬎0.05). The decrease of summary depression of the ST-segment (EST) was registered while using irbesartan (6.44⫾1.22 to 5.32⫾0.34 mm, -17.4%, p⬍0.001) and valsartan (5.81⫾0.21 to 5.08⫾0.14 mm, -12.6%, p⬍0.01) with the increase tendency for eprosartan (5.50⫾0.27 to 5.26⫾0.13 mm, -9.6%, p⬎0.05). It’s found out that the antiischemic effect of the antihypertensive drugs - antagonists of angiotensine II (AT1) receptors can be connected with the decrease of vessels ␣-adrenoreceptors activity and the improvement of myocardial metabolism, the interlock of angiotensine II on the level of coronary vessels, which is accompanied by the betterment of coronary blood circulation. Key Words: essential hypertension, antagonists of AT1-receptors, transoesophageal electrocardiostimulation
P-261 THE SENSITIVITY OF THE BARORECEPTOR REFLEX IN SPONTANEOUSLY HYPERTENSIVE RATS IS INCREASED BY CHRONIC VASOPEPTIDASE INHIBITION Alexandra Thornagel, Andreas Dendorfer, Walter Raasch, Peter Dominiak. Institute of exp. & clin. Pharmacology and Toxicology, University Clinic of Luebeck, Luebeck, Germany. The new class of combined inhibitors of Angiotensin-Converting Enzyme (ACE) and Neutral Endopeptidase (NEP) named vasopeptidase inhibitors has a potential effect on the sympathetic nervous system by influencing the degradation pathways of many neurotransmitters in the central nervous system (CNS). For some of them (i.e. the natriuretic peptides) it is shown that they can modulate the activity of the sympathetic nervous system. To demonstrate the significance of NEP in this respect, we investigated the baroreceptor sensitivity (BRS) in rats chronically treated with a vasopeptidase inhibitor compared with single inhibition of ACE. Spontaneously hypertensive rats (SHR) were treated orally for 17 days either with placebo, ramipril (1mg/kg) or the vasopeptidase inhibitor omapatrilat (30 mg/kg). On day 16, heart rate variability (HRV) was tested during 30min of silence followed by 3 min noise stress (white noise, 60 dBA) in conscious rats. For examination of BRS, the mean arterial pressure (MAP) was altered by infusion of phenylephrine and sodium-nitroprussid and the responding changes in heart rate (HR) were determined. The next day, rats were anaesthetized with pentobarbital (60 mg/kg, i.p.), and the splanchnic nerve was prepared for extracellular recording of sympathetic nerve activity (SNA). The response of SNA to blood pressure alterations (range: 50-200 mmHg MAP) was detected. Ramipril or omapatrilat induced equivalent long-term reductions in systolic blood pressure (-18.4 and –23.1 mmHg vs. placebo, respectively) and in plasma ACE activity (-81.9%, and -72.7% vs. placebo, respectively). In conscious rats, neither HR nor HRV under basal as well as noise stress conditions, was influenced by treatment. Maximum suppres-
POSTERS: Antihypertensive Drugs
AJH–May 2003–VOL. 16, NO. 5, PART 2
P-255 EFFECTS OF A FIXED-DOSE ACE INHIBITORDIURETIC COMBINATION ON AMBULATORY BLOOD PRESSURE AND ARTERIAL PROPERTIES IN ISOLATED SYSTOLIC HYPERTENSION: COMPARISON WITH CALCIUM CHANNEL BLOCKER AND DIURETIC THERAPY Joanne M Ferguson, Jack Minas, Siky Siapantas, Paul A Komesaroff, Krishnankutty Sudhir. Hormones and Vasculature Laboratory, Baker Medical Research Institute, Melbourne, VIC, Australia; Center for Cardiovascular Interventions, Stanford University, Palo Alto, CA. The ideal therapy for patients with isolated systolic hypertension (ISH) is unclear; diuretics, calcium channel blockers (CCB’s) and ACE inhibitors are all used in clinical practice. Ambulatory blood pressures (ABP) are superior to clinic BP in ISH as predictors of cardiovascular risk. ISH is characterized by increased arterial stiffness, also a predictor of cardiovascular events. We hypothesized that a fixed-dose ACE-inhibitor/diuretic combination would reduce ABP and arterial stiffness in ISH more than monotherapies. Using a double-blind, randomized, cross-over design, the effects of 8 wks of Fosinopril/Hydrochlorothiazide combination (FOS-HCT, 10/12.5mg, titrated up to 20/12.5mg) were compared with CCB (AMLO, Amlodipine, 5mg titrated up to 10mg) and diuretic (INDA, Indapamide, 2.5mg) monotherapy in 28 patients with ISH (mean BP 165/86⫾2/1). Each patient received all 3 therapies with a 2 wk washout period in between; treatment order was randomly selected. Effects of therapy were assessed on 24h ABP, clinic BP, and applanation tonometry-derived augmentation index, a measure of wave reflection and an indirect marker of vascular stiffness. At 8 wks, the fall in average 24h systolic BP (SBP) and night-time SBP were greater in the FOS-HCT group, compared to AMLO and INDA (Table). The decrease in augmentation index was also greater in the FOS-HCT group, compared to AMLO (Table). There was no difference between therapies in their effects on clinic systolic (p⫽0.23) or diastolic BP (p⫽0.22), a.m. measurements made 2-3 hrs after dosing of antihypertensive therapy, nor on diastolic ABP, (24h, diurnal or nocturnal). Thus, compared with either CCB or diuretic therapy a fixed-dose ACE-inhibitor/diuretic combination induces greater reductions in systolic ABP, particularly at night, favorable effects that may be related to a decrease in the intensity of, or delay in, arterial wave reflections. ACE-inhibitor/diuretic combination therapy is thus a useful approach to cardiovascular risk reduction in ISH. Reduction in 24h, Day, and Night Systolic ABP (mmHg) and Augmentation Index (%) Variable
FOS/HCT
AMLO
INDA
P Value
⌬24h SysABP ⌬Day SysABP ⌬Night SysABP ⌬Aug. Index
17 ⫾ 2 16 ⫾ 2 18 ⫾ 2 10.3 ⫾ 1.9
14 ⫾ 1 15 ⫾ 2 13 ⫾ 2 3.6 ⫾ 2.1
12 ⫾ 1 13 ⫾ 2 12 ⫾ 2 6.6 ⫾ 1.4
0.005 0.432 0.021 0.035
Key Words: isolated systolic hypertension, ACE inhibitors, Diuretics
P-256 L- PLUS N- TYPE CA2ⴙ CHANNEL BLOCKER CILNIDIPINE REDUCED ARRHYTHMOGENIC SUBSTRATES IN THE CANINE SUDDEN CARDIAC DEATH MODEL WITH HYPERTENSION Akira Takahara, Atsushi Sugiyama, Yoshioki Satoh, Yuji Nakamura, Tomoyuki Konda, Keitaro Hashimoto. Pharmaceutical Research Laboratories, Pharmaceuticals Company, Ajinomoto Co., Inc, Kawasaki, Kanagawa, Japan; Department of Pharmacology, University of Yamanashi Faculty of Medicine, Tamaho, Yamanashi, Japan. The chronic atrio-ventricular (AV) conduction block dog has been used as a sudden cardiac death model complicating systemic hypertension, of which arrhythmogenic substrates can be potentiated by both endogenous neurohumoral factors like epinephrine and drugs such as IKr inhibitors. In
this study, we assessed the effects of a vascular L- and sympathetic N-type Ca2⫹ channel blocker cilnidipine on hemodynamic, electrophysiological and neurohumoral parameters in this model to estimate its new clinical application. Cilnidipine in a dose of 5mg/day was orally administered to the AV block dogs for 4 weeks. Holter ECG, cardiohemodynamic variables and the monophasic action potential (MAP) duration were measured before and 4 weeks after the start of drug administration (n⫽7). Cilnidipine decreased the mean blood pressures from 144⫾6 to 118⫾10 mmHg. Also, cilnidipine increased the cardiac output from 1.7⫾0.1 to 2.4⫾0.3 l/min, decreased the plasma epinephrine concentration from 305⫾43 to 201⫾40 pg/ml, shortened MAP duration from 270⫾16 to 233⫾12 msec, and decreased the number of premature ventricular contractions from 284⫾177 to 25⫾16 beats/21 hr. These results suggest that cilnidipine decreased the blood pressure, reduced plasma epinephrine level and promoted the ventricular repolarization process of the AV block dogs, which would be possibly exerted through both L- and N-type Ca2⫹ channel inhibitions. Thus, 4 weeks administration of cilnidipine can reduce the arrhythmogenic substrates of the canine sudden cardiac death model. Key Words: calcium channel blocker, arrhythmia
P-257 LEVAMLODIPINE THERAPY FOR HYPERTENSION AFTER KIDNEY TRANSPLANTATION S. D. Tang, J. Qi, Z. W. Han, Z. L. Ming. Shanghai Institute of Hypertension, Rui jin Hospital, Shanghai, P.R., China. Hypertension after kidney transplantation in a special type of secondary hypertension which is a risk factor for the development of complications of hypertension such as renal failure. Apart from control of blood pressure, levamlodipine (levogyral Amlodipine), a long-acting calcium blocker has been shown to protect renal function, 20 cases (M:15,F:5, age 43⫾11.3 years. Range 22-60) were been randomly selected from kidney transplantation patients, all previous antihypertension medication was discontinued before the start of the study. A baseline sitting diastolic blood pressure of ⱖ95mmHg and ⱕ114mmHg and systolic blood pressure of ⱕ190mmHg at the end of dismedication were taken as criteria for study entry. The duration of active treatment with levamlodipine was two months. The initial dose give was 2.5mg levamlodipine as a once-daily dose, after one month of treatment with 2.5mg levamlodipine, patients not responding to this dose regimen received 5mg as a once-daily dose for a further one month treatment. Responders to 2.5mg Levamlodipine continued to take the same dose until the end of the study, after two months of active treatment, SBP, DBP, blood nitrogen decrease obviously (P⬍0.01, ⬍0.01, ⬍0.01, ⬍0.05), while the serum creatine and the blood cyclosporin concentration are not increase (P⬎0.05), without affecting to blood lipids, serum K⫹, serum Na⫹, serum C1-, serum uric acid. Monotherapy with levamlodipine in a dose range of 2.5-5mg oncedaily achieved normalization of blood pressure in 85% hypertension patients after kidney transplantation, at the same time, renal function were improved. Key Words: Levamlodipine, Kidney, Transplantation
P-258 EFFICACY OF ANGIOTENSIN II ANTAGONISTS IN TREATMENT OF ESSENTIAL HYPERTENSION ASSOCIATED WITH ISCHEMIC HEART DISEASE Victor K. Tashchuk, Tatiana O. Kulik. Dept.of Cardiology, Bukovinian State Medical Academy, Chernivtsy, Chernivtsy District, Ukraine; Dept.of Cardiology, Bukovinian State Medical Academy, Chernivtsy, Chernivtsy District, Ukraine. The aim of the investigation was to study the effect of irbesartan (a highly selective angiotensin II antagonist) and its influence on coronary reserve
AJH–May 2003–VOL. 16, NO. 5, PART 2
and functional state of myocardium in patients with essential hypertension in combination with stable angina pectoris. Stress-echocardiography (EchoCG) under the conditions of transesophageal electrocardiostimulation (TEES) was performed and 24-hour Holter ECG monitoring (HM) was recorded in 172 patients (98 men, mean age 52.2⫾1.8 years) before and after 4 week treatment period with irbesartan (80 mg/day orally). Under the irbesartan action the frequency of the cessation of TEES increased from 138.4⫾2.2 to 149.6⫾1.4 imp/min (p⬍0.001), while the summary ST-segment depression decreased from 4.86⫾0.22 to 3.12⫾0.13 mm (p⬍0.001). The results of EchoCG have testified the increase of ejection fraction (EF) at rest from 50.1⫾0.7 to 58.5⫾0.8 % (p⬍0.001). The decrease of EF at peak of TEES was -10.5 % at the beginning and -3.2 % at the end of irbesartan treatment period. According to the data of HM, irbesartan significantly reduced the frequency (from 2,1⫾0.3 to 1,3⫾0.1 episodes, p⬍0.01) and the total duration of painful ischemic episodes (from 37.3⫾5.5 to 20.5⫾4.6 minutes, p⬍0.02). The same tend was registered for silent ischemic episodes: the frequency decreased from 3,3⫾0.5 to 2,5⫾0.4 episodes (p⬎0.2) and total duration from 51.7⫾6.4 to 42.1⫾4.8 minutes (p⬎0.2). Thus, the results show that irbesartan treatment has positive effect on coronary reserve and improves myocardial contractility in patients with essential hypertension associated with ischemic heart disease. Key Words: essential hypertension, irbesartan, ischemic heart disease
P-259 AMLODIPINE: INFLUENCE ON REGIONAL MYOCARDIAL CONTRACTILITY Victor K. Tashchuk, Pavlo R. Ivanchuk, Ivanna A. Tashchuk. Dept. of Cardiology, Bukovinian State Medical Academy, Chernivtsy, Chernivtsy District, Ukraine; Dept. of Cardiology, Bukovinian State Medical Academy, Chernivtsy, Chernivtsy District, Ukraine; Dept. of Cardiology, Bukovinian State Medical Academy, Chernivtsy, Chernivtsy District, Ukraine. In order to determinate the efficiency of amlodipine’s (Pfizer) influence on the capability of the left ventricular (LV) myocardial contractility, 40 patients with essential hypertension and ischemic heart disease (stable angina pectoris) were examined after the dynamic contractility of the left ventricle myocardium was tested. Patients were examined during the acute period of the amlodipine test and under the background of 10 days of treatment. Clinical effect of amlodipine is related to the blood pressure stabilization. In average on 3rd day of treatment, amlodipine lead to systolic blood pressure decrease up to 24,7% (p⬍0.05) and diastolic blood pressure decrease up to 24,2% (p⬍0.05). Bicycle ergometry was carried out until clinical and diagnostic criteria were reached, the test was stopped when 92,2% out of the calculated sub maximum load was carried out. Echocardiography at that point failed to show any substantial dynamics of the volume indexes and the general ejection fraction (GEF). On the other hand analyses of the regional ejection fraction (REF) testify, that the use of amlodipine, already during the acute period of testing, lead to it’s improvement, the changes were authentic for REF8 (p⬍0.05), in other regions of the left ventricle, increase myocardial contractility tendencies were noted. Initial parameters of the regional contractility in terms of the 10 days amlodipine treatment, regional contractility profile changing tendencies was characterized with decrease for the REF3-5 and increase of the REF1-2, REF6-12, changes for REF1 were authentic (p⬍0.05). At the height of the recurring amlodipine test, compared to the initial amlodipine test, similar change tendencies were registered along with the increase of the initial REF1-2 and REF6-12 in view of REF3-5 decrease. Thus, it is defined that amlodipine, even in a short treatment term, possesses positive influence on the regional contractility. Key Words: essential hypertension, amlodipine, regional contractility
POSTERS: Antihypertensive Drugs
131A
P-260 ANTAGONISTS OF ANGIOTENSINE RECEPTORS AND ACUTE STRESS-TEST : POSSIBILITY IN TREATMENT OF HYPERTENSION Victor K. Tashchuk, Svetlana I. Grechko. Dept. of Cardiology, Bukovinian State Medical Academy, Chernivtsy, Chernivtsy District, Ukraine; Dept. of Cardiology, Bukovinian State Medical Academy, Chernivtsy, Chernivtsy District, Ukraine. 46 patients who had essential hypertension on background concomitant ischemic heart disease were examined with the aim of study the antiischemic effect of antagonists of angiotensine II (AT1) receptors (irbesartan, valsartan and eprosartan), using pair stress-test – transoesophageal electrocardiostimulation (TEES). The frequency of TEES cessation increased using valsartan (130.1⫾1.5 to 135.3⫾2.1 imp/min, ⫹4,0%, p⬍0.05), insignificantly in case of irbesartan usage (135.4⫾2.4 to 140.6⫾1.8 imp/min, 3,9%, p⬎0.05) and eprosartan (127.6⫾1.8 to 131.5⫾1.4 imp/min, 3,1%, p⬎0.05). The decrease of summary depression of the ST-segment (EST) was registered while using irbesartan (6.44⫾1.22 to 5.32⫾0.34 mm, -17.4%, p⬍0.001) and valsartan (5.81⫾0.21 to 5.08⫾0.14 mm, -12.6%, p⬍0.01) with the increase tendency for eprosartan (5.50⫾0.27 to 5.26⫾0.13 mm, -9.6%, p⬎0.05). It’s found out that the antiischemic effect of the antihypertensive drugs - antagonists of angiotensine II (AT1) receptors can be connected with the decrease of vessels ␣-adrenoreceptors activity and the improvement of myocardial metabolism, the interlock of angiotensine II on the level of coronary vessels, which is accompanied by the betterment of coronary blood circulation. Key Words: essential hypertension, antagonists of AT1-receptors, transoesophageal electrocardiostimulation
P-261 THE SENSITIVITY OF THE BARORECEPTOR REFLEX IN SPONTANEOUSLY HYPERTENSIVE RATS IS INCREASED BY CHRONIC VASOPEPTIDASE INHIBITION Alexandra Thornagel, Andreas Dendorfer, Walter Raasch, Peter Dominiak. Institute of exp. & clin. Pharmacology and Toxicology, University Clinic of Luebeck, Luebeck, Germany. The new class of combined inhibitors of Angiotensin-Converting Enzyme (ACE) and Neutral Endopeptidase (NEP) named vasopeptidase inhibitors has a potential effect on the sympathetic nervous system by influencing the degradation pathways of many neurotransmitters in the central nervous system (CNS). For some of them (i.e. the natriuretic peptides) it is shown that they can modulate the activity of the sympathetic nervous system. To demonstrate the significance of NEP in this respect, we investigated the baroreceptor sensitivity (BRS) in rats chronically treated with a vasopeptidase inhibitor compared with single inhibition of ACE. Spontaneously hypertensive rats (SHR) were treated orally for 17 days either with placebo, ramipril (1mg/kg) or the vasopeptidase inhibitor omapatrilat (30 mg/kg). On day 16, heart rate variability (HRV) was tested during 30min of silence followed by 3 min noise stress (white noise, 60 dBA) in conscious rats. For examination of BRS, the mean arterial pressure (MAP) was altered by infusion of phenylephrine and sodium-nitroprussid and the responding changes in heart rate (HR) were determined. The next day, rats were anaesthetized with pentobarbital (60 mg/kg, i.p.), and the splanchnic nerve was prepared for extracellular recording of sympathetic nerve activity (SNA). The response of SNA to blood pressure alterations (range: 50-200 mmHg MAP) was detected. Ramipril or omapatrilat induced equivalent long-term reductions in systolic blood pressure (-18.4 and –23.1 mmHg vs. placebo, respectively) and in plasma ACE activity (-81.9%, and -72.7% vs. placebo, respectively). In conscious rats, neither HR nor HRV under basal as well as noise stress conditions, was influenced by treatment. Maximum suppres-