Genetic correlations between the cumulative pseudo-survival rate, milk yield, and somatic cell score during lactation in Holstein cattle in Japan using a random regression model.

Trends in genetic correlations between longevity, milk yield, and somatic cell score (SCS) during lactation in cows are difficult to trace. In this study, changes in the genetic correlations between milk yield, SCS, and cumulative pseudo-survival rate (PSR) during lactation were examined, and the effect of milk yield and SCS information on the reliability of estimated breeding value (EBV) of PSR were determined. Test day milk yield, SCS, and PSR records were obtained for Holstein cows in Japan from 2004 to 2013. A random subset of the data was used for the analysis (825 herds, 205,383 cows). This data set was randomly divided into 5 subsets (162-168 herds, 83,389-95,854 cows), and genetic parameters were estimated in each subset independently. Data were analyzed using multiple-trait random regression animal models including either the residual effect for the whole lactation period (H0), the residual effects for 5 lactation stages (H5), or both of these residual effects (HD). Milk yield heritability increased until 310 to 351 d in milk (DIM) and SCS heritability increased until 330 to 344 DIM. Heritability estimates for PSR increased with DIM from 0.00 to 0.05. The genetic correlation between milk yield and SCS increased negatively to under -0.60 at 455 DIM. The genetic correlation between milk yield and PSR increased until 342 to 355 DIM (0.53-0.57). The genetic correlation between the SCS and PSR was -0.82 to -0.83 at around 180 DIM, and decreased to -0.65 to -0.71 at 455 DIM. The reliability of EBV of PSR for sires with 30 or more recorded daughters was 0.17 to 0.45 when the effects of correlated traits were ignored. The maximum reliability of EBV was observed at 257 (H0) or 322 (HD) DIM. When the correlations of PSR with milk yield and SCS were considered, the reliabilities of PSR estimates increased to 0.31-0.76. The genetic parameter estimates of H5 were the same as those for HD. The rank correlation coefficients of the EBV of PSR between H0 and H5 or HD were greater than 0.9. Additionally, the reliabilities of EBV of PSR of H0 were similar to those for H5 and HD. Therefore, the genetic parameter estimates in H0 were not substantially different from those in H5 and HD. When milk yield and SCS, which were genetically correlated with PSR, were used, the reliability of PSR increased. Estimates of the genetic correlations between PSR and milk yield and between PSR and SCS are useful for management and breeding decisions to extend the herd life of cows.

Genetic analysis of the cumulative pseudo-survival rate during lactation of Holstein cattle in Japan by using random regression models.

Longevity is a crucial economic trait in the dairy farming industry. In this study, our objective was to develop a random regression model for genetic evaluation of survival. For the analysis, we used test-day records obtained for the first 5 lactations of 380,252 cows from 1,296 herds in Japan between 2001 and 2010; this data set was randomly divided into 7 subsets. The cumulative pseudo-survival rate (PSR) was determined according to whether a cow was alive (1) or absent (0) in her herd on the test day within each lactation group. Each lactation number was treated as an independent trait in a random regression multiple-trait model (MTM) or as a repeated measure in a random regression single-trait repeatability model (STRM). A proportional hazard model (PHM) was also developed as a piecewise-hazards model. The average (± standard deviation) heritability estimates of the PSR at 365 d in milk (DIM) among the 7 data sets in the first (LG1), second (LG2), and third to fifth lactations (LG3) of the MTM were 0.042±0.007, 0.070±0.012, and 0.084±0.007, respectively. The heritability estimate of the STRM was 0.038±0.004. The genetic correlations of PSR between distinct DIM within or between lactation groups were high when the interval between DIM was short. These results indicated that whereas the genetic factors contributing to the PSR between closely associated DIM would be similar even for different lactation numbers, the genetic factors contributing to PSR would differ between distinct lactation periods. The average (± standard deviation) effective heritability estimate based on the relative risk of the PHM among the 7 data sets was 0.068±0.009. The estimated breeding values (EBV) in LG1, LG2, LG3, the STRM, and the PHM were unbiased estimates of the genetic trend. The absolute values of the Spearman's rank correlation coefficients between the EBV of the relative risk of the PHM and the EBV of PSR at 365 DIM for LG1, LG2, LG3, and the STRM were 0.75, 0.87, 0.91, and 0.93, respectively. These results indicated that the EBV of PSR could predict the genetic contribution to survival. The EBV based on the PSR of the STRM was highly correlated with that of the MTM (0.83-0.96). Furthermore, the calculation load of the STRM was lighter than that of the MTM because the rank of the matrix of the STRM was smaller than that of the MTM. These results indicated that the STRM is an appropriate model for estimating survivability by using random regression models.

Association between ovocalyxin-32 gene haplotypes and eggshell quality traits in an F2 intercross between two chicken lines divergently selected for eggshell strength.

Broken and cracked eggshells contribute significantly to economic losses in the egg production industry. We previously identified ovocalyxin-32 as a potential gene influencing eggshell traits, by analysing an intercross between two parent lines developed from the same founder population by a two-way selection for eggshell strength with non-destructive deformation (DEF) conducted over 14 generations. We determined the nucleotide sequences of six ovocalyxin-32 exons in the parent individuals and analysed the association between ovocalyxin-32 and eggshell traits in the F2 individuals. We identified three haplotypes (W, M and S) of ovocalyxin-32 in the parent individuals. A mismatch amplification mutation assay was performed to distinguish six diplotype individuals (WW, MM, SS, WM, MS and WS) inthe F2 population. The egg weight (EW) of SS-diplotype individuals was significantly higher than that of WW-, WM- and WS-diplotypes. Short length of the egg (SLE) of SS-diplotype individuals was significantly higher than that of WW-, WM- and MS-diplotypes. Long length of the egg (LLE) of SS-diplotype individuals was significantly higher than that of WM and WS-diplotypes. DEF of WW-diplotype individuals was significantly higher than that ofSS-, WM, MS and WM-diplotypes. Haplotypic effect analyses showed significant differences between the W-haplotype and the S-haplotypes in the EW, SLE, LLE and DEF. The DEF of M-haplotype was significantly lower than that of W- and S-haplotypes. These results suggest that S- and M-haplotypes are critical for high quality of eggshells in the F2 population. In conclusion, ovocalyxin-32 is a useful marker of eggshell traits and can be used to develop strategies for improving eggshell traits in commercial layer houses.

Mapping of quantitative trait loci affecting eggshell quality on chromosome 9 in an F(2) intercross between two chicken lines divergently selected for eggshell strength.

Broken and cracked eggshells are major causes of significant economic losses to the egg production industry. The quantitative trait loci (QTL) on chromosome 9 influencing the quality of eggshells were identified by analysing an intercross between two parent lines developed from the same founder population by a two-way selection for eggshell strength with non-destructive deformation conducted over 14 generations. Chromosome-wide highly significant (P < 0.01) QTL associated with egg weight (EW), short length of egg (SLE), long length of egg (LLE) and eggshell weight were mapped to the distal region of chromosome 9. Among the QTL affecting EW, SLE and LLE, ovocalyxin-32 was identified as a potential candidate gene influencing eggshell traits. Marker-assisted selection based on these QTL could be used to develop strategies for reducing the breakage and cracking of eggs in commercial layer houses.

Polymorphism of the ovocalyxin-32 gene and its association with egg production traits in the chicken.

We performed candidate gene analysis to identify SNP in the chicken ovocalyxin-32 (OCX-32) gene in the F(2) resource population, to develop a PCR-RFLP method for genotyping and to evaluate the associations of the gene polymorphism with egg production traits. The F(2) resource population-comprising 272 chickens-was obtained by crossing White Leghorn (WL) males and Rhode Island Red (RIR) females. They were measured for egg production traits and used for candidate gene analysis. Among parental individuals of the F(2) population, 2 novel nonsynonymous polymorphisms (c.267T>G and c.494A>C) and 1 known nonsynonymous polymorphism (c.381G>C) in the coding sequences of the chicken OCX-32 gene were detected. The PCR-RFLP method was used for screening the chickens of the F(2) population. In parental populations, genotype c.267T>G and c.494A>C were segregated within WL and RIR breeds, respectively, but genotype c.381G>C was breed-specific SNP between WL and RIR breeds. A total of 4 haplotypes were constructed based on the 3 SNP in parental populations, and there was no recombination between c.267T>G and c.494A>C. There was a significant association (P < 0.05) between the OCX-32 gene SNP and egg production traits, but there was no significant association between the haplotypes of the OCX-32 gene and egg production traits in the F(2) population. In the present study, there was the most significant association between c.381G>C of the OCX-32 gene and rate of egg production. The current study is the first step to confirm the relationship between OCX-32 gene polymorphisms and egg production traits.

Genetic mapping of quantitative trait loci affecting growth and carcass traits in F2 intercross chickens.

We constructed a chicken F(2) resource population to facilitate the genetic improvement of economically important traits, particularly growth and carcass traits. An F(2) population comprising 240 chickens obtained by crossing a Shamo (lean, lightweight Japanese native breed) male and White Plymouth Rock breed (fat, heavyweight broiler) females was measured for BW, carcass weight (CW), abdominal fat weight (AFW), breast muscle weight (BMW), and thigh muscle weight (TMW) and was used for genome-wide linkage and QTL analysis, using a total of 240 microsatellite markers. A total of 14 QTL were detected at a 5% chromosome-wide level, and 7 QTL were significant at a 5% experiment-wide level for the traits evaluated in the F(2) population. For growth traits, significant and suggestive QTL affecting BW (measured at 6 and 9 wk) and average daily gain were identified on similar regions of chromosomes 1 and 3. For carcass traits, the QTL effects on CW were detected on chromosomes 1 and 3, with the greatest F-ratio of 15.0 being obtained for CW on chromosome 3. Quantitative trait loci positions affecting BMW and TMW were not detected at the same loci as those detected for BMW percentage of CW and TMW percentage of CW. For AFW, QTL positions were detected at the same loci as those detected for AFW percentage of CW. The present study identified significant QTL affecting BW, CW, and AFW.

Sensitivity of planktic foraminiferal test bulk density to ocean acidification.

The anthropogenic CO2 accumulating in the ocean is lowering seawater carbonate ion concentration and may reduce calcification rates of marine calcareous organisms. Several proxies based on test weights of planktic foraminifera have been used to evaluate the impact of ocean acidification on these organisms. Unfortunately, because of the absence of a method to evaluate the bulk density of a test, the impact of seawater carbonate chemistry on test calcification is still not fully understood. In this study, we measured bulk densities of living Globigerina bulloides (planktic foraminifera) tests with an X-ray micro-computed tomography (XMCT) scanner and compared them with ambient seawater characteristics. Results demonstrated that test bulk densities were controlled by ambient seawater carbonate ion concentrations and that changes of test bulk densities were accompanied by changes in micron to submicron scale porosity of internal ultrastructure. These results suggest that alteration of the bulk density of foraminiferal tests due to acidification of ambient seawater can be directly observed by XMCT scanning. A useful metric of calcification intensity would therefore be physical measurements of test densities with XMCT.

Dissociation of changes in cardiovascular mass and performance with angiotensin-converting enzyme inhibitors in Wistar-Kyoto and spontaneously hypertensive rats.

The effects of angiotensin-converting enzyme inhibitors on cardiovascular mass and function were measured in three groups of 22 week old male Wistar-Kyoto normotensive and spontaneously hypertensive rats treated with CGS-16617, cilazapril or quinapril. Left ventricular performance was assessed by electromagnetic flow meter during rapid whole blood infusion before and after arterial pressure and increased abruptly with aortic snare; aortic distensibility also was assessed in vitro. The systemic hemodynamic effects of these three agents were similar, yet their structural effects varied. Although left ventricular and aortic masses diminished and right ventricular mass remained unchanged (with all three agents) in the spontaneously hypertensive rats, CGS-11617 and cilazapril also reduced left ventricular mass in the normotensive Wistar-Kyoto rats without changing aortic mass. All three agents improved aortic distensibility whether or not mass was decreased. Left ventricular structural changes were associated with variable changes in pumping ability. These data show that reduced mass associated with angiotensin-converting enzyme inhibitor treatment was not consistent in ventricles and aorta, that a dissociation exists between structural and functional changes and that reduction of cardiac mass alone does not relate to changes in chamber mass or in function. Thus, biologic and pharmacodynamic differences exist among angiotensin-converting enzyme inhibitors as well as between classes of antihypertensive agents.

Effect of beta-blockers on circulating levels of inflammatory and anti-inflammatory cytokines in patients with dilated cardiomyopathy.

OBJECTIVES: This study was designed to evaluate the beneficial effect of beta-blockers on circulating cytokine levels in patients with dilated cardiomyopathy (DCM). BACKGROUND: Elevated circulating levels of inflammatory cytokines have been reported in patients with DCM. However, alterations of the levels of inflammatory and anti-inflammatory cytokines in association with beta-blocker therapy are unknown. METHODS: We studied 32 patients with idiopathic DCM who had been treated with digitalis, diuretics and angiotensin-converting enzyme inhibitors. In addition to this combination therapy, beta-blockers were started in all patients. Serum levels of interleukin (IL)-10, tumor necrosis factor-alpha (TNF-alpha) and soluble TNF receptors (sTNF-R1 and R2) were measured at baseline and 12 weeks after the initiation of beta-blocker therapy. We also measured plasma levels of neurohumoral factors, as well as left ventricular (LV) size and function. Ten age-matched subjects with no cardiac disease served as the control group. RESULTS: Baseline levels of IL-10, TNF-alpha and sTNF-R2 were significantly higher in patients with DCM than in control subjects (p < 0.05). There was a significant positive correlation between IL-10 and TNF-alpha levels (r = 0.545, p = 0.029). The TNF-alpha/IL-10 ratio correlated well with plasma epinephrine levels (r = 0.677, p = 0.025), and the level of sTNF-R2 was closely related to LV size. Serum levels of IL-10, TNF-alpha and sTNF-R2 were significantly decreased during beta-blocker therapy (p < 0.005). CONCLUSIONS: Our findings indicate that beta-blockers have an important immunoregulatory role in modifying the dysregulated cytokine network in DCM. This effect of beta-blockers may be partly responsible for the efficacy of therapeutic drugs for heart failure.

Evaluation of intrarenal hemodynamics by Doppler ultrasonography for renoprotective effect of angiotensin receptor blockade.

AIMS: It has been shown that both angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II type 1 receptor blockers (ARB) have renoprotective effects via mechanisms that are independent of blood pressure reduction. The aim of this study was to evaluate the intrarenal hemodynamic change with ARB by renal Doppler ultrasonography (RDU) and to assess the mechanism of ARB in patients with hypertension. METHODS: Thirty hypertensive patients with renal insufficiency caused by glomerular diseases, diabetes and hypertensive nephrosclerosis were included in this study. RDU was performed before and one week after taking ARB. Resistance index (RI) (peak systolic velocity - end diastolic velocity/peak systolic velocity) in the intrarenal segmental artery were calculated, and the amounts of urinary protein or albumin were determined. RESULTS: We defined patients whose microalbuminuria or proteinuria was reduced by greater than 30% by ARB as responders (n = 22) and defined other patients as non-responders (n = 8). There were no significant differences between the responder and non-responder groups in baseline characteristics. RI was significantly improved by ARB in the responder group, but not in the non-responder group. The reduction of RI after ARB treatment was most prominent in patients with hypertensive nephrosclerosis. CONCLUSIONS: Improvement in intrarenal hemodynamics might play an important role in the mechanisms of the renoprotective effect of ARB in patients with hypertension.

Hemostatic activation in spontaneous intracerebral hemorrhage.

BACKGROUND AND PURPOSE: There is no in-depth information available on the changes in hemostatic systems in patients in the acute phase of spontaneous intracerebral hemorrhage (ICH). This study was conducted to assess the relationships between the changes in hemostatic systems and clinical parameters in patients in acute-phase ICH. METHODS: The records of 358 patients admitted within 6 hours of onset of ICH were reviewed to examine the relationships between changes in hemostatic systems and computed tomographic findings and clinical parameters. RESULTS: -The white blood cell counts and the levels of thrombin-antithrombin complex, plasmin-antiplasmin complex, and D-dimer in patients with intraventricular extension (IVE) or subarachnoid hemorrhage (SAH) were significantly (P<0.05) higher than those in patients without IVE or SAH. Most of the hemostatic system parameters in patients without IVE or SAH showed no significant differences compared with normal subjects. Multiple linear regression analysis revealed that the levels of thrombin-antithrombin complex significantly increased with an increase in the amount of SAH (P<0.001) and IVE (P<0.001). The levels of thrombin-antithrombin complex were not significantly associated with the volume of intraparenchymal hematoma. The level of the complex, however, was significantly (P<0.001) and independently associated with the presence of IVE or SAH (multiple logistic regression analysis). CONCLUSIONS: The systemic activation of hemostatic systems in ICH patients seems to take place only when blood reaches the subarachnoid space. The intraparenchymal hematoma itself seems unlikely to activate hemostatic systems in peripheral blood, although the hematoma is expected to cause local activation of hemostatic systems.

Management of hypertension in high school students by using new salt titrator tape.

In a blood pressure screening program involving 6589 high school students, 180 male (4.7%) and 17 female (0.6%) students were identified as borderline hypertensive. The 174 hypertensive male adolescents studied further showed pathophysiological features such as a significantly higher frequency of obesity, higher 24-hour urinary sodium excretion, higher hematocrit value, higher sodium and lower potassium concentration in red blood cells, and higher ouabain-sensitive sodium efflux compared with the control group (231 male students; p less than 0.05). When used alone, the ordinary 10-week period of counseling about a low salt diet failed to significantly reduce the blood pressure of hypertensive students. However, when education and counseling efforts were combined with self-monitoring of salt (chloride) excretion in overnight urine samples using a new salt titrator tape developed in our laboratory, 24-hour urinary sodium excretion, weight, and blood pressure decreased significantly over 10 weeks (mean reduction: 52 mEq/day for 24-hour urinary sodium excretion, 1.7 kg for weight, 12/7 mm Hg for blood pressure). These results indicate that blood pressure of borderline hypertensive adolescents could be effectively reduced with this nonpharmacological method of dietary education. Such systematic management might be of importance for the prevention of essential hypertension.

Clinical and physiologic significance of local tissue renin-angiotensin systems.

Increasing and compelling evidence continues to amass that favors the existence of local tissue renin-angiotensin systems. All renin-angiotensin system components have been demonstrated in kidney, brain, arteries, adrenals, and other organs. Favoring its clinical importance are direct demonstration of its components in tissues; dissociation between hemodynamic and structural effects of renin-angiotensin system inhibition; evidence for local modulating roles with other humoral, autocrine/paracrine, and growth factors; and the effects of renin-angiotensin system inhibitors in patients who are anephric or have low plasma renin activity. Evidence will be presented demonstrating the hemodynamic/structural dissociation of pharmacologic agents that reduce cardiac mass in spontaneously hypertensive rats with left ventricular hypertrophy. Although centrally active adrenolytic agents, angiotensin-converting enzyme inhibitors, and calcium antagonists all reduce cardiac mass, their structural and cardiac functional effects differ greatly. Even within the angiotensin-converting enzyme inhibitor group their effects vary: improving, impairing, or not changing the Frank-Starling relationships. It is postulated that there is great variability of cardiac intramyocytic penetration of the pharmacologic agents and of their local intracellular effects on mitogenesis. The implications for cardiac function and therapy are vast.

Changes in cardiovascular mass, left ventricular pumping ability and aortic distensibility after calcium antagonists in Wistar-Kyoto and spontaneously hypertensive rats.

OBJECTIVES: To determine the effects of different dihydropyridine calcium antagonists on cardiovascular mass and function in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). METHODS: The rats were treated daily for 3 weeks with nitrendipine (20 mg/kg), nifedipine (30 mg/kg), nisoldipine (6 mg/kg) or their vehicles. At the conclusion of that period left ventricular pumping ability and aortic distensibility were determined, and the aortic, cardiac and left and right ventricular masses. RESULTS: Each drug reduced arterial pressure in both rat strains; each decreased left ventricular mass in SHR but not in WKY rats. All three agents increased right ventricular mass in WKY rats; only nisoldipine did so in SHR. Each compound improved left ventricular pumping ability in WKY rats, maintaining function even when pressure was abruptly increased to pretreatment levels. In contrast, although all three calcium antagonists improved cardiac performance in SHR at the pharmacologically reduced pressures, pumping ability was not maintained when pressure was increased to pretreatment levels in nisoldipine-treated SHR. All three agents improved aortic distensibility in both strains, but only in SHR was reduced aortic mass demonstrated. CONCLUSIONS: These data not only continue to demonstrate a functional/structural dissociation associated with antihypertensive therapy, but also suggest subtle functional and structural effects that differ even within the same class of calcium antagonists.

Antigen dependent release of interleukin 5 in vitro from spleen cells of mice infected with Angiostrongylus cantonensis.

The kinetics of eosinophil growth and/or survival stimulating factors (Eo-stimulating factors) released by spleen cells from A. cantonensis-infected mice were assessed by in vitro marrow cultures. When spleen cells from C57BL/6 mice 8 to 20 days p.i. were cultured with young adult A. cantonensis worm antigen or Con A, almost equal amounts of Eo-stimulating factors were detected in the conditioned media obtained from both stimulations. No Eo-stimulating factor activity was detected in cultures from spleen cells without stimulation or from normal spleen cells with stimulation. Production of Eo-stimulating factors was inhibited by the pretreatment of the spleen cells with anti-Thy1.2 or anti-L3T4 antibodies plus complement but not with anti-Lyt2.2 antibody. In the presence of anti-mouse IL-5 monoclonal antibody, the activity of Eo-stimulating factors was inhibited by up to 99%. IL-5, therefore, appears to play a principal role in induction of eosinophilia in mice infected with A. cantonensis.

Protection of pigs against mosquito-borne Japanese encephalitis virus by immunization with a live attenuated vaccine.

Pigs were vaccinated with an attenuated Japanese encephalitis virus (JEV) vaccine and challenged with virulent JEV, either by subcutaneous injection or by exposure to infected mosquitoes. The vaccinated pigs developed circulating antibodies to JEV. After challenge they did not develop viremia detectable by inoculation of their serum in suckling mice. They were also unable to transmit virus to mosquitoes fed on their skin. In contrast, unvaccinated pigs, whether challenged by injection or by mosquito bites, developed viremia and did transmit virus to mosquitoes which were allowed to bite them. Transmission seemed possible for only 3 days post-infection.

Experimental gastric carcinoma induced by N-methyl-N'-nitro-N-nitrosoguanidine.

Serial studies by endoscopy and biopsy were made in a Beagle dog during and after oral administration of N-methyl-N'-nitro-N-nitroguanidine (MNNG). Between the 23rd and the 45th week of observation erosions and ulcers appeared at the angulus of the stomach and turned into ulcer scar. A depression with atypical glands was seen in the ulcer scar of the posterior wall of the angulus at the 94th week. It developed elevated margins at the 102nd week, when a well differentiated adenocarcinoma was found histopathologically. Ulceration and reepithelialization were observed in the early carcinoma. The carcinoma progressed into a larger one of Borrmann's type 2 at the 115th week and further into its type 3 at the 181st week. A second carcinoma with signet ring cell carcinoma developed in the anterior wall of the angulus. The two carcinomas fused and formed a single lesion. At autopsy in the 216th week the carcinoma invaded the serosa, and metastasis to regional lymph nodes was observed.

DNA cytophotometry on atypical glands in stomach carcinogenesis of dogs induced by N-methyl-N'-nitro-N-nitrosoguanidine.

Microspectrophotometric measurement of the DNA content of cell nuclei was performed on the lesions (including atypical glands) in gastric carcinogenesis of 15 male beagle dogs, which had been induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The distribution patterns of DNA content were classified into three types: normal, subnormal, and abnormal. The histograms of the distribution in normal and regenerative glands were a normal type and subnormal type, respectively, while adenocarcinoma showed an abnormal distribution type. In atypical glands, the distribution patterns in autopsy cases were subnormal and abnormal types. When sequential endoscopic observation of the angulus of the stomach in dog No. 3 was carried out, atypical glands were found in an ulcer in the early stage of MNNG administration and a precancerous lesion in the late stage after termination of MNNG. The atypical glands in the early stage were of the subnormal type, while the atypical glands in the late stage were of the abnormal type. According to the results, these two types-subnormal and abnormal - of distribution of DNA content on the atypical glands may be related to regeneration and subsequent development of cancer, respectively.

A study of the effects of delapril, a new angiotensin converting enzyme inhibitor, on the diurnal variation of arterial pressure in patients with essential hypertension using indirect and direct arterial pressure monitoring methods.

In order to investigate the effect of delapril, a new angiotensin converting enzyme inhibitor, on the diurnal variation of arterial pressure in patients with essential hypertension, this study examined 24 h arterial pressure using an indirect or a direct monitoring system. When the effect of twice-a-day administration of delapril at daily doses of 30 to 90 mg was examined using the indirect monitoring system in 12 outpatients, delapril decreased systolic and diastolic arterial pressures significantly only at limited points during the day. However, each of the averaged 24 h daytime and nighttime arterial pressures showed significant reductions. The 24 h intraarterial pressure monitoring demonstrated that delapril decreased systolic and diastolic arterial pressure at most of the measurement points. The arterial pressure reductions during daytime and nighttime were not significantly different, that is, there was no excessive reduction in nighttime arterial pressure. Heart rate and its variability were virtually unaffected by the delapril treatment in either monitoring study. No adverse reactions were observed in the indirect or direct monitoring studies. Thus, it is concluded that twice-a-day administration of delapril at daily doses of 30 to 90 mg brings about a safe and stable antihypertensive effect, without affecting the diurnal variation of arterial pressure.