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The purpose of this study was to investigate the causes for the differences observed in the pharmacokinetics of YJA-20379-8 in 16-week-old spontaneously hypertensive rats (SHRs). To see if the hereditary characteristics of SHRs was the cause, 20 mg/kg of the drug was intravenously infused over 15 min and 50 mg/kg of the drug was orally administered to 6-week-old SHRs and 16-week-old SHRs and their age-matched control Kyoto-Wistar (KW) rats. Also to see if the hypertensive status itself was the cause, the same doses were administered to 16-week-old deoxycorticosterone acetate (DOCA) salt-induced hypertensive rats (DOCA-salt rats) and their age-matched control Sprague-Dawley rats. The areas under the plasma concentration-time curve from time zero to time infinity (for intravenous study) and to the last sampling time in plasma (for oral study) were significantly smaller after both intravenous and oral administration, and the total body clearances of the drug were significantly faster after intravenous administration to 6-week-old SHRs, 16-week-old SHRs, and 16-week-old DOCA-salt rats than those in their respective age-matched control rats. The above pharmacokinetic parameter changes in 16-week-old SHRs were due to both hereditary characteristic of SHRs and the hypertensive status itself., (Copyright 2000 John Wiley & Sons, Ltd.)

Recent studies have found the tryptophan allele of a glycine to tryptophan polymorphism at position 460 (G460W) of the alpha-adducin protein to be associated with essential hypertension in European populations. We examined whether the tryptophan allele is associated with hypertension in a different population, comprised of subjects of Chinese origin from Taiwan, and Chinese and Japanese origin from the San Francisco Bay area and Hawaii. We adapted the 5' allelic discrimination assay or TaqMan to type individuals for the G460W polymorphism, and using this method we typed more than 1000 individuals. The frequency of the W allele was slightly increased in the treated subjects in the Chinese population (0.458 v 0.423) but not the Japanese population (0.549 v 0.558). We considered dominant, recessive, and additive models in our analysis. There was a significant result for a recessive model for systolic blood pressure in the Chinese population (chi2 6.84, df = 2, P < .05), but only suggestive evidence for diastolic blood pressure (chi2 3.30). In contrast, in the Japanese population, there was no evidence for a positive association under any model. For the combined Chinese and Japanese samples, the evidence for association with alpha-adducin was not significant.

Background: Irbesartan is a newly developed angiotensin II receptor antagonist. Its antihypertensive efficacy and safety in Taiwanese patients with mild to moderate hypertension remains to be determined., Methods: This was a multicenter, double-blind, randomized, parallel group study. One hundred and sixteen patients from three centers were enrolled. After a placebo lead-in period of 14 days, 55 patients (24-75 years-of-age) who had a mean seated diastolic blood pressure of 95 to 110 mmHg were randomized to once-daily treatment with irbesartan 150 mg or enalapril 10 mg. Doses were doubled at week 4 if trough seated diastolic blood pressure was 90 mmHg or more. Trough blood pressure was measured at zero, two, four and eight weeks of treatment., Results: Both treatments lowered blood pressure with no significant difference in efficacy between treatment groups. Irbesartan 150 mg to 300 mg provided reductions in trough seated systolic and diastolic blood pressures at week 8 of -16.5 mmHg and -7.2 mmHg, respectively, with 36% of patients having a favorable response. Similarly, enalapril 10 mg to 20 mg reduced systolic and diastolic blood pressure by -10.6 mmHg and -5.0 mmHg, respectively, with a response rate of 43%. Headache, malaise and dizziness were the major adverse reactions observed in both groups. The incidence of drug-related cough was significantly higher with enalapril (18%) than with irbesartan (0%)., Conclusions: Irbesartan 150 mg to 300 mg once daily was as effective in lowering blood pressure as enalapril 10 mg to 20 mg once daily. Both irbesartan and enalapril were well tolerated, while there was a significantly lower incidence of cough with irbesartan compared with enalapril.

Objective: The goals of this study were to compare glucose tolerance in dipper and nondipper hypertensive patients and to explore the cause of glucose intolerance in essential hypertension., Research Design and Methods: A total of 50 patients <45 years old who had essential hypertension were recruited and studied by 24-h blood pressure monitoring and an oral glucose tolerance test (OGTT). Autonomic function was assessed with spectral analysis of heart rate variability, Results: Dipper hypertensive patients (n=25) had lower nocturnal blood pressure than nondipper (n=25) patients. During OGTT, postprandial glucose levels were higher in the nondippers at 0, 90, and 120 min (all P < 0.05). Nondippers had a higher fasting insulin/glucose ratio than was apparent in normal control subjects. Despite higher postprandial glucose levels, nondippers had lower postprandial insulin levels. These results suggest that nondippers were insulin resistant and that their pancreatic beta-cell function was impaired. For all patients, nocturnal reduction of blood pressure was inversely related to total glucose levels under the OGTT curve and was positively related to postprandial insulin levels. Daytime heart rate did not differ between the dippers and nondippers, but nocturnal heart rate was higher in the nondippers, suggesting that nocturnal sympathetic activities were higher among the nondippers. Spectral analysis of heart rate variability suggests that the nondippers had lower parasympathetic activities and unbalanced sympathetic/parasympathetic outflow., Conclusions: These findings indicate that nondipper hypertensive patients are more glucose intolerant than are dipper patients. The abnormalities of glucose metabolism in nondippers could be explained by insulin resistance and beta-cell dysfunction. The results of spectral analysis suggest that abnormal autonomic outflow may represent a possible link between hypertension and associated metabolic dysfunction.

This article reviews our work on the effects of different classes of antihypertensive agents on the hemodynamic alterations in essential human hypertension. Short-term studies were done during cardiac catheterization in young normotensive subjects (mean age, 33 years; range, 19 to 40) and several different age-matched (range, 25 to 53 years) groups of patients with essential hypertension. Aortic impedance, resistance, wave reflections, and compliance were calculated from high-fidelity recordings of ascending aortic pressure and flow signals during baseline and after nitroprusside, propranolol followed by phentolamine, phentolamine, captopril, and nifedipine, respectively, at doses sufficient to normalize blood pressure in each hypertensive group. Propranolol exacerbated all the hemodynamic parameters; these effects were only partially overcome by phentolamine. Among the other agents only phentolamine did not completely normalize compliance, and only captopril did not completely normalize wave reflections. The long-term study was a randomized, double-blind comparison of fosinopril and atenolol in 79 normotensive subjects and 79 essential hypertensive patients. Baseline 24-hour ambulatory blood pressures and carotid artery tonometry to index wave reflections were performed in all subjects and in hypertensive patients after 8 weeks of therapy. Both fosinopril and atenolol normalized blood pressure and lowered the elevated augmentation index, but fosinopril had a significantly larger effect than atenolol. Both short- and long-term beta-blockade did not have as beneficial an effect as the other agents. Thus, the differing hemodynamic effects of the various classes of antihypertensive agents might be a consideration in the choice of therapy.

Background: Benazepril hydrochloride is a non-sulfhydryl-containing, angiotensin-converting enzyme (ACE) inhibitor. The short-term and long-term antihypertensive effects of benazepril remain to be established in Chinese., Methods: Hypertensive subjects with diastolic blood pressure 95-110 mmHg, after two week placebo run-in first, entered a four-week double-blind phase with treatment of benazepril 10 mg once daily or captopril 25 mg three times daily, then received one-year open treatment of benazepril 10 mg daily with or without diuretics. Ambulatory blood pressure monitoring was performed at the end of placebo run-in, after four-week double-blind phase, and after one-year open treatment., Results: Of the 75 subjects (41 male, 34 female, mean age 57 +/- 12 years, range 34-88 years) who completed the double-blind phase, 42 subjects finished the one-year extension phase. Reasons for withdrawal from the study included irritable cough (16, 21%), hypotension (1, 1%), and poor compliance (16, 21%). During the short-term double-blind phase, benazepril reduced clinic and mean 24-h ambulatory blood pressure by -21/-10 mmHg and by -17/-10 mmHg respectively, and captopril by -21/-13 mmHg and by -17/-10 mmHg respectively. After one-year open treatment by benazepril for the 42 subjects, the one-year average clinic blood pressure was 134/88 mmHg (155/104 mmHg at entry and 135/93 mmHg at the end of the double-blind phase), and the mean 24-h ambulatory blood pressure was 137/87 mmHg (149/95 mmHg at entry and 132/84 mmHg at the end of the double-blind phase)., Conclusions: The antihypertensive effect of benazepril 10 mg daily with or without diuretics is not significantly different from that of captopril 75 mg daily in the short-term and can reasonably be maintained for one year.

Previous studies have shown some distinct hemodynamic alterations in essential hypertension, including increased resistance, wave reflections, and pulse wave velocity and decreased arterial compliance. These abnormalities are completely normalized by nonspecific smooth muscle dilation with nitroprusside but not by combined alpha- and beta-adrenergic blockade or angiotensin-converting enzyme inhibition, suggesting an enhanced smooth muscle tone that cannot be attributed solely to the sympathetic nervous or renin-angiotensin systems. Since hypertensive patients have an enhanced calcium influx-dependent vasoconstriction, we performed the present study to examine the extent to which the dihydropyridine calcium channel antagonist nifedipine could normalize the hemodynamic abnormalities in essential hypertension. An essential hypertensive patient group was compared with a normotensive group similar in age, body size, and proportion of men and women. During diagnostic cardiac catheterization, ascending aortic micromanometer pressures and electromagnetic flows were measured at baseline and after sufficient sublingual nifedipine (mean, 24 mg) to normalize blood pressure. From the pressures and flows, aortic input impedance, wave reflection magnitude, and compliance were computed. In the hypertensive group, the hemodynamic alterations were indistinguishable from those summarized above. Nifedipine produced sufficient vasodilation to completely normalize all of these hemodynamic alterations, including wave reflections. From these results, together with those reported in our previous studies, it is clear that the various classes of antihypertensive agents affect hemodynamics differently. All are capable of decreasing blood pressure to normotensive levels, but only nitroprusside and nifedipine can also completely normalize all the other pulsatile hemodynamic alterations. Thus, these hemodynamic effects of the different classes of antihypertensive agents should be considered in choosing a therapeutic modality.

We conducted this study to compare the effects of fosinopril versus atenolol on peripheral blood pressure, central arterial wave reflection, and left ventricular mass in a group of patients with essential hypertension. We conducted a double-blind, randomized trial of fosinopril and atenolol in 79 hypertensive patients (52 men, 27 women; mean age, 45.8 +/- 8.5 years; range, 30 to 68 years). Carotid pressure waveforms were recorded noninvasively by applanation tonometry with a Millar micromanometer-tipped probe. The extent of wave reflection was estimated by the augmentation index defined as the ratio of the amplitude of pressure wave above its systolic shoulder to the pulse pressure. The augmentation index, left ventricular mass index by two-dimensional echocardiography, and 24-hour ambulatory blood pressures were determined before and after 8 weeks of daily treatment with fosinopril (10 to 20 mg) or atenolol (50 to 100 mg) with or without diuretics and compared with those values in 79 normotensive control subjects. After 8 weeks of treatment, both drugs lowered 24-hour ambulatory peripheral systolic and diastolic pressures into the normal range to a similar extent (fosinopril, -18/-13 mm Hg; atenolol, -23/-17 mm Hg, both P = NS). On the other hand, whereas the elevated augmentation index in hypertensive patients compared with normotensive subjects (16 +/- 11% versus 10 +/- 8%) was completely normalized by fosinopril (-9.3 +/- 9.8%, P < or = .002), it was lowered by atenolol (-4.8 +/- 8.9%, P < .002) but to a significantly smaller extent (fosinopril versus atenolol effect, P = .04).(ABSTRACT TRUNCATED AT 250 WORDS)

Data on the prevalence and predictors of hypertension in Kinmen, an island very close to southern mainland China but under Republic of China administration, would be very helpful to understand the effect of environmental and psychosocial factors on hypertension in a specific ethnic group. In 1991, Kin-Hu residents > or = 30 years of age, living in the second largest township of Kinmen, were invited to participate in this survey incorporating face-to-face interviews with a structured questionnaire, collection of fasting blood samples and oral glucose tolerance test. The response rate for subjects with complete data was 80.3% (3289 of 4097). The prevalence rates for definite hypertension (> or = 160/95 mm Hg and/or under antihypertensive treatment) were 20.1, 14.0, and 16.9% for men, women, and the total population, respectively. Overall awareness, treatment, and control rates of definite hypertension were 46.9, 25.0, and 4.7%, respectively. According to the final logistic regression model, after controlling for all other covariates, the significant predictors for current-definite hypertension were old age, male sex, nonsmoking, obesity, alcohol intake, high waist-to-hip ratio, high serum triglyceride and high serum uric acid levels. In comparison with Chinese in Taiwan and mainland China, the unexpectedly high prevalence of hypertension and distinct set of its predictors in Kin-Hu form the basis for future study.

We report a 20-year-old female with severe hypertension, hypokalemia, hyperaldosteronism and elevated level of plasma renin activity (PRA). The clinical diagnosis of renin secreting tumor of left kidney was made before surgery by the lateralization of plasma renin activity via selective renal venous blood sampling and CT scan of kidney. Prompt normalization of blood pressure and decrease of PRA and aldosterone levels were found after surgical removal of the tumor. The pathological findings showed a juxtaglomerular cell tumor.

Previous studies have shown some distinct hemodynamic alterations in essential hypertension, including increased resistance, wave reflections, and pulse wave velocity and decreased systemic compliance. These abnormalities are completely normalized by nonspecific smooth muscle dilation with nitroprusside but not by combined alpha- and beta-adrenergic blockade. The renin-angiotensin system, acting possibly via both circulating and local tissue effects, is thought to play an important role in essential hypertension, so its role in the altered hemodynamics deserves careful investigation. A hypertensive patient group was compared with a normotensive group similar in age, body size, and proportion of men and women. During diagnostic cardiac catheterization, ascending aortic micromanometer pressures and electromagnetic flows were measured in the baseline state. Intravenous captopril of a sufficient dosage (11 mg) to normalize blood pressure then was given to the hypertensive patients while measurements were repeated. From the pressures and flows, aortic input impedance, wave reflection magnitude, and compliance were computed. In the hypertensive group, the important hemodynamic alterations consisted of increased peripheral resistance, first zero crossing of aortic impedance phase angle, and wave reflections and decreased systemic compliance. Captopril had a pronounced hemodynamic effect. It normalized blood pressure, resistance, and impedance phase angle zero crossing. Compliance, although increased substantially by captopril, was still slightly lower than normotensive levels. The magnitude of wave reflections, although substantially lowered by angiotensin converting enzyme inhibition, was still persistently greater than normal. The present results, together with those previously reported, demonstrate that a complex interplay of factors underlies the increased smooth muscle tone in essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this placebo-control, double-blind, randomized and crossover study is to evaluate the effect of nicardipine and nifedipine in Chinese senile hypertension. Among totally 37 senile hypertensive patients enrolled, 26 patients (25 males, 1 female) from 55 to 78 years of age (mean 65) who had finished one part or whole protocol were studied. Totally 18 cases after 6-week treatment of nicardipine (Perdipine) had blood pressure decrease significantly from 152.6 +/- 12.3/99.6 +/- 5.7 to 140.4 +/- 15.6/93.8 +/- 8.1 mmHg in supine position (P < 0.05), and from 153.3 +/- 12.7/98.7 +/- 7.7 to 139.2 +/- 13.5/90.7 +/- 7.6 mmHg in standing position (p < 0.05). Twenty-five cases after 6-week treatment of nifedipine (Towarat) also had significant blood pressure decrease from 155.0 +/- 13.3/99.5 +/- 8.4 to 144.2 +/- 10.0/95.3 +/- 9.2 mmHg in supine position (P < 0.05), and from 151.5 +/- 17.8/100.6 +/- 9.5 to 138.6 +/- 12.8/90.4 +/- 8.3 mmHg in standing position (p < 0.05). Heart rate was unchanged in both groups. Both nicardipine and nifedipine decreased blood pressure and increased heart rate significantly with the first dose of medication in the morning (P < 0.05). There was 6.5% and 9.0% decrease of systolic and diastolic blood pressure with nicardipine in supine position, 10.1% and 11.2% decrease with nifedipine in supine position, 6.3% and 7.2% decrease with nicardipine in standing position, and 9.7% and 10.6% decrease with nifedipine in standing position. The major side-effects were palpitation (20%) and lower abdominal distension (16%) with nicardipine; and nausea or vomiting (22%) and dizziness (15%) with nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

A community-based study was carried out by the Yang-Ming Crusade in 1987-1988 in Pu-Li Town, Taiwan. We interviewed 1738 out of 2573 registered residents more than 30 years old and their fasting blood samples were drawn and tested. The prevalences of definite hypertension (greater than or equal to 160/95 mm Hg) and borderline hypertension (140/90 to 160/95 mm Hg) were 18.7% and 16.0%, respectively. To study factors associated with hypertension, univariate analysis was applied first. Stratified analyses by age and sex were used for interaction assessment. Logistic regression was used for multivariate analysis. According to the final model, the significant factors related to definite hypertension were age (greater than or equal to 50 v less than 50 years of age, odds ratio [OR] 2.6, 95% confidence interval [CI] 1.6 to 4.3), physical activity (frequent v infrequent, OR 0.4, 95% CI 0.2 to 0.6), alcohol intake (yes v no, OR 2.3, 95% CI 1.1 to 4.6), and cholesterol (greater than or equal to 240 v less than 240 mg/dL, OR 1.7, 95% CI 1.0 to 2.9). Significant factors related to borderline hypertension were age (only for those cholesterol greater than or equal to 240 mg/dL, greater than or equal to 50 v less than 50 years of age, OR 4.1, 95% CI 2.1 to 7.9), cholesterol (only for those age less than 50, greater than or equal to 240 v less than 240 mg/dL, OR 3.6, 95% CI 1.6 to 7.8), physical activity (frequent v infrequent, OR 0.4, 95% CI 0.2 to 0.7), and alcohol intake (yes v no, OR 2.3, 95% CI 1.1 to 4.6).(ABSTRACT TRUNCATED AT 250 WORDS)

Background: This study tested whether the simple ratio of ventricular end-systolic pressure to stroke volume, known as the effective arterial elastance (Ea), provides a valid measure of arterial load in humans with normal and aged hypertensive vasculatures., Methods and Results: Ventricular pressure-volume and invasive aortic pressure and flow were simultaneously determined in 10 subjects (four young normotensive and six older hypertensive). Measurements were obtained at rest, during mechanically reduced preload, and after pharmacological interventions. Two measures of arterial load were compared: One was derived from aortic input impedance and arterial compliance data using an algebraic expression based on a three-element Windkessel model of the arterial system [Ea(Z)], and the other was more simply measured as the ratio of ventricular end-systolic pressure to stroke volume [Ea(PV)]. Although derived from completely different data sources and despite the simplifying assumptions of Ea(PV), both Ea(Z) and Ea(PV) were virtually identical over a broad range of altered conditions: Ea(PV) = 0.97.Ea(Z) + 0.17; n = 33, r2 = 0.98, SEE = 0.09, p less than 0.0001. Whereas Ea(PV) also correlated with mean arterial resistance, it exceeded resistance by as much as 25% in older hypertensive subjects (because of reduced compliance and wave reflections), which better indexed the arterial load effects on the ventricle. Simple methods to estimate Ea (PV) from routine arterial pressures were tested and validated., Conclusions: Ea(PV) provides a convenient, useful method to assess arterial load and its impact on the human ventricle. These results highlight effects of increased pulsatile load caused by aging or hypertension on the pressure-volume loop and indicate that this load and its effects on cardiac performance are often underestimated by mean arterial resistance but are better accounted for by Ea.

The clinical significance of isolated systolic hypertension (systolic blood pressure greater than or equal to 160 mmHg and diastolic blood pressure less than 90 mmHg) has long been recognized, but its prevalence and correlates have not been well characterized. A community-based study was carried out by the Yang-Ming Crusade in 1987-1988 in Pu-Li Town, Taiwan. Of the 2573 registered residents over 30 years old, 1738 were interviewed, and their fasting blood samples were drawn and tested. The prevalence of isolated systolic hypertension was 2.1%. Age-specific prevalence increased with age. No significant difference was found between men and women. No trend was found at the urbanizational level. To study the significant correlates of isolated systolic hypertension, univariate analyses were applied first. Stratified analyses by age and by sex were used for interaction assessment. Based on the above findings as well as from the clinical point of view, logistic regression was used for multivariate analyses. Logistic regression analysis showed that after controlling the covariates simultaneously, four variables were significantly correlated with isolated systolic hypertension: age (greater than or equal to 50 vs. less than 50 years, OR = 3.4, 95% CI = 1.6-7.2); diabetes (yes vs. no, OR = 2.4, 95% CI = 1.2-4.7); blood urea nitrogen (greater than or equal to 25 vs. less than 25 mg/dl, OR = 2.1, 95% CI = 1.2-3.9); and physical activity (frequent vs. infrequent, OR = 1.8, 95% CI = 1.0-3.1). In comparison with definite (greater than or equal than 160/95 mmHg) and borderline (140/90-160/95 mmHg) hypertension as defined by WHO, the different sets of predictors and the possible adverse effect of frequent physical activity on isolated systolic hypertension were found and discussed.

Background: Resistance, pulse wave velocity, and wave reflections have been shown to be increased in patients with essential hypertension compared with normotensive controls. These alterations are completely normalized by nitroprusside infusion but exacerbated during beta-adrenergic blockade, suggesting an enhanced smooth muscle tone that is in part modulated by adrenergically mediated vasodilation. The present study was performed to examine the extent to which this apparently enhanced smooth muscle tone is a result of alpha-adrenergically mediated vasoconstriction., Methods and Results: Age-matched normotensive and hypertensive Chinese subjects were instrumented with catheter-tipped micromanometers and an electromagnetic flow velocity sensor positioned in the ascending aorta. Aortic impedance and wave reflection properties were obtained from Fourier analysis of the pressure and flow signals during baseline conditions, after beta-blockade with propranolol (0.15 mg/kg i.v.), and after alpha-blockade with intravenous phentolamine (range, 15-80 mg) that was sufficient to either normalize blood pressure or produce a pressure that could not be further lowered. Compared with normotensives, in the baseline state, hypertensives had elevated resistance (1,962 versus 1,268 dyne.sec/cm5, p less than 0.001), total power (1,893 versus 1,568 mW, p less than 0.08), reflected pressure wave component (25.6 versus 13.5 mm Hg, p less than 0.001), ratio of reflected to forward wave (0.65 versus 0.42, p less than 0.001), and pulse wave velocity as determined from the frequency of the first zero-crossing of impedance phase angle (4.6 versus 3.5 Hz, p less than 0.03). During combined alpha- and beta-adrenergic blockade, blood pressure decreased into the normal range (from 162/103 to 131/87 mm Hg) but was still somewhat higher than that in the normotensive subjects. Resistance (1,914 dyne.sec/cm5, p less than 0.03), reflected wave (19.5 mm Hg, p less than 0.01), and ratio of reflected to forward wave (0.61, p less than 0.001) were, however, persistently elevated above normal values., Conclusions: alpha-Adrenergically mediated vasoconstriction cannot account for all of the hemodynamic alterations seen in essential hypertension.

Study Objective: The aim was to compare regional wave transmission and reflection properties along the aorta in age matched normotensive and hypertensive subjects., Design: Simultaneous upstream and downstream micromanometer pressures were recorded at five regions from the ascending aorta to the iliac artery. Recordings were made in the baseline condition in both groups and during sustained isometric handgrip exercise in the normotensives to see if increasing the blood pressure to hypertensive levels would eliminate baseline differences between the two groups., Subjects: Only subjects who had no coronary or valvular heart disease were studied. Normotensive subjects (n = 8) were selected from those undergoing electrophysiological testing whose blood pressures were consistently in the normal range (systolic less than 140, diastolic less than 90 mm Hg). Age matched hypertensive subjects (n = 17) were those in whom secondary causes of hypertension were excluded and who had repeated measurements of raised blood pressure., Measurements and Results: In each region pulse wave velocity was estimated from the simultaneous upstream and downstream pressure records using the foot to foot method, and apparent phase velocity was obtained from Fourier analysis of the two pressures. The intensity of wave reflections was judged by the magnitude of fluctuations of the harmonics of apparent phase velocity about the mean of the higher frequency harmonics. In both groups in the baseline state there were regional variations in the pulse wave velocity with the lowest values occurring just proximal to the renal arteries and highest values occurring in the iliac artery. Likewise, in both groups the extent of wave reflections varied regionally--pronounced reflections were seen in the ascending aorta and from just proximal to the renal arteries to the aortic bifurcation but not in the mid-thoracic or iliac regions. The hypertensives had higher pulse wave velocity than normotensives only in the iliac artery (780 v 567 cm.s-1) and had more reflections in the three regions in which reflections were evident. Although handgrip in the normotensive group eliminated regional differences in pulse wave velocity between the groups, reflections were still greater in the hypertensives., Conclusions: Essential hypertension affects the regional properties of the aortic wall. These alterations are manifested by increased peripheral wave-speed and increased wave reflections along the aorta. The differences in wavespeed but not reflection properties are eliminated when the pressures are matched by handgrip, suggesting that factors other than the level of blood pressure per se are responsible for the alterations in reflection properties.

Differences in aortic impedance between normotensives and hypertensives are not well characterized. We examined impedance in 8 normotensive and 11 hypertensive (mean 96.7 vs. 122.2 mmHg) age-matched, Chinese patients undergoing cardiac catheterization at rest, during nitroprusside, and handgrip exercise before and after beta blockade (propranolol). Hypertensives had higher resistance (2,295 vs. 1713 dyn-s/cm5), characteristic impedance (145.7 vs. 93.9 dyn-s/cm5), total external power (1,579 vs. 1174 mW), peripheral reflections (ratio of backward to forward wave components of 0.54 vs. 0.44), and first zero crossing of impedance phase angle (4.15 vs. 2.97 Hz). These abnormalities were eliminated with vasodilatation. Differences between groups were not further exacerbated when pressure was increased during handgrip exercise. Beta blockade further increased resistance and reflections. Thus, hemodynamic abnormalities of essential hypertension (increased resistance, reflections, and pulse wave velocity, and decreased compliance) are compatible with an increased vasomotor tone that is further unmasked during generalized beta blockade.

Objective: This study evaluated the steady-state pharmacokinetics and dose proportionality of fosinopril in Chinese patients with congestive heart failure in an open-label, randomised, three-way crossover study design. Patients: Chinese patients with congestive heart failure (NYHA class II or III, ejection fraction ≤ 40%) were enrolled from three hospitals in Taiwan. Interventions: Immediately following a lead-in period of fosinopril 10mg daily, patients received three consecutive oral dosage regimens of fosinopril (10, 20 or 40mg once daily) for 10 to 14 days per period without intervening washout periods. Serum and urine were analysed for fosinoprilat (the pharmacologically active diacid) concentrations by liquid chromatography/tandem mass spectrometry. Results: All treatment periods were completed by 23 patients. Five patients experienced adverse events of numbness, syncope, oedema or mouth ulcers that were possibly related to fosinopril. Heart disease was considered the cause of sudden death in one patient 19 days after completion of the study. At all doses, fosinopril almost completely inhibited serum ACE activity. Statistical analysis of pharmacokinetic data showed no significant differences among doses in any of the following parameters: dose-adjusted maximum serum concentration (C) and area under the serum concentration-time curve values (as assessed by 90% confidence intervals of the mean ratios at steady-state), time to reach C, serum elimination half-life, cumulative urinary excretion (expressed as a percentage of the administered dose), and renal clearance. At the higher dose levels, there was a somewhat greater fluctuation in steady-state fosinoprilat concentrations. Conclusion: Fosinopril is a potent, well-tolerated ACE inhibitor in Chinese patients with mild to moderate heart failure, and exhibited dose-proportional pharmacokinetics in the 10 to 40mg dose range. [ABSTRACT FROM AUTHOR]