Relation between Pulse Wave Velocity, Left Ventricular Diastolic Function, and Circadian Variation of Blood Pressure in Patients with Never Treated Essential Hypertension

BACKGROUND AND OBJECTIVES: An increased pulse wave velocity (PWV) and a non-dipping pattern in hypertensive patients have been shown to be associated with an excess of target organ damage. The relationship between the PWV and circadian variation of blood pressure (BP) (dipper or nondipper) were sought, and also the LV diastolic function between dipper and nondipper patients compared. SUBJECTS AND METHODS: 44 hypertensive subjects, who had never been treated, were enrolled (mean age: 48+/-12 yrs, men: 29). The following procedures were undertaken. 1) 24 hour ambulatory BP monitoring; 2) echocardiography for LV geometry, LV mass index (LVMI), LV systolic and diastolic functions, including tissue Doppler and aortic PWV. The patients were divided into two groups with respect to their ambulatory BP profiles, i.e., dipper and nondipper. The PWV, LV geometry and diastolic functions were compared between dipper and nondipper patients, and the relationship between the PWV and diastolic function analyzed in all patients. RESULTS: Twenty (45%) were nondipper patients. There were no significant differences in the LV geometry, LVMI and PWV between dipper and nondipper patients (PWV; 8.8+/-3.1 vs. 8.6+/-3.3 m/sec, p>0.05). In all patients, the PWV was related to the deceleration time (r=0.34, p=0.03) and the mitral E/A (r=-0.31, p=0.02) and mitral Em/Am ratios obtained by the tissue Doppler echocardiography (r=-0.31, p=0.03). The proportion with diastolic dysfunction was higher in the nondipper than the dipper patients (21 vs. 50%, p<0.01). There was a significant relation between the PWV and Em (r=-0.45, p=0.047) in the nondipper, but not in the dipper. CONCLUSION: Prolonged exposure to high BP (nondipper) was not related with increased aortic stiffness in never treated hypertensive patients. The PWV was closely related with LV diastolic dysfunction in nondipper patients.

Effect of L-Arginine on Post-Ischemic Myocardial and Vascular Stunning in Open-Chest Dogs

BACKGROUND: Although recent studies have demonstrated that infusion of L-arginine reduces myocardial necrotic area during prolonged ischemia, its effects on transient postischemic myocardial dysfunction(myocardial stunning) and microvascular dyfunction(vascular stunning) are not well known. To investigate whether intravenous administration of L-arginine, physiological nitric oxide(NO) precursor, during reperfusion would attenuate postischemic myocardial dysfunction and microvascular dysfunction, 15 open-chest dogs were studied. METHODS: In 15 pentobarbital anesthesized open-chest dogs, left circumflex coronary artery was occluded for 20 minutes and was followed by a reperfusion for 60 minutes. L-Arginine(30mg/kg)(L-arginine group, n=8) or saline(control group, n=7) was given intravenously by a bolus 1 minute before reperfusion and was followed by a continuous infusion(10mg/kg/min) for 30 minutes during reperfusion. Before coronary occlusion and 60 minutes after reperfusion, coronary blood flow(CBF) and coronary vascular resistance(CVR) wre measured after intracoronary injection of each of acetylcholine(0.01/kg) and adenosine(1.5/kg), and reactive hyperemia with coronary occlusion(RH20) for 20 seconds was measured. Myocardial segment thickening in the area of ischemia-reperfusion was measured using 2D-echocardiography. The echocardiographic images were digitized and analyzed by cardiac image analyzer. RESULTS: The results obtained 60 minutes after reperfusion were as follows. 1) CBF was decreased by 41% in L-arginine group vs 30.1% in control group(p < 0.05) and CVR was increased by 83.9% in L-arginine group vs 19.3% in control group after 60 minutes of reperfusion, compared with pre-occlusion baseline values. 2) Percent change of CBF was decreased in control group(acetylcholine by 25.8%, adenosine by 29.2%, RH20 by 39.8%), while it was increased in L-arginine group(acetylcholine by 60%, adenosine by 22%, RH20 by 26.7%). Percent change of CVR was increased in control group(acetylcholine by 10.5%, adenosine by 6.9%, RH20 by 21%), but it was decreased in L-arginine group(acetylcholine by 10%, adenosine by 6.6%, RH20 by 1.6%). Increase of CBF and decrease of CVR were significant on acetylcholine and RH20 between control group and L-arginine group. 3) Fraction of myocardial segment thickening was significantly decreased in L-arginine group(by 80%) compared with control group(by 61.7%, p < 0.05). CONCLUSIONS: The finding that L-arginine depressed post-ischemic myocardial contractil function suggests that systemic infusion of L-arginine has unfavorable effect on myocardial stunning. In contrast, the finding that L-arginine improved CBF and CVR with acetylcholine and adenosine and reactive hyperemia indicates that L-arginine may exert a beneficial effect on vascular stunning. These results suggest that L-arginine may have independent effects on myocardial stunning and vascular stunning.

Clinical Effect and Safety of Celiprolol in Patients with Essential Hypertension

BACKGROUND: Celiprolol is a new generation beta-adrenoreceptor blocking agent with intrinsic sympathomimetic activity characterized by selective blockade of beta1 receptors and partial agonist activity at beta2 receptors. This study was designed to investigate the antihypertensive efficacy and safety of celiprolol in patients with essential hypertension. METHODS: The study subjects consisted of 36 patients(mean age : 55 years, 11 males, 25 females). Celiprolol was administered orally in a aily dose of 200-800mg once or two divided dose for 10 weeks after the admimstration of placebo for 2 weeks. RESULTS: Blood pressure was significantly reduced from 171+/-19/106.8mmHg to 153+/-20/92+/-12mmHg(p<0.01) after 2 week of therapy and this effect was maintained throughout the study periods. The efficacy rates were total 94%(marked improve : 53%, moderate improve : 22%, mild improve : 19%). The cumulative efficacy rate was 72% at 200mg/day, 91% at 400mg/day, and 94% at 800mg/day. Heart rate did not change throughout 10 weeks. There were no significant change in hematologic and blood chemistry variables. During the period of medication, headache developed in 3 cases(8%) and each of dry cough, dyspnea, epigastric pain and diarrhea and facial flushing developed in 1 case(2.8%) but they were tolerable. CONCLUSIONS: This results suggest that celiprolol is effective and safe drug in the treament of patients with essential hypertension.