Synthesis of water-soluble anthracene-appended benzoxaboroles and evaluation of their cis-1,2-diol recognition properties.

Three series of water-soluble anthracene-appended benzoxaboroles 1a-c were developed; their binding affinity toward cis-1,2-diols was explored by conventional fluorescence titrations to demonstrate the role of benzoxaborole as a general recognition motif of cis-1,2-diols for fluorescent probes. The complex structures of the tetra-coordinated boronate adducts between 1 and the cis-1,2-diols were revealed.

Questionable expression of unstable DQ heterodimer containing HLA-DQA1*01:07.

Human leukocyte antigens (HLA)-DQA1*01:07 was identified as an HLA-DQ blank specificity that segregated with the serological HLA-A2, -B7, -DR14, -DR52 haplotype, which carried DQB1*05:03. The blank specificity of DQA1*01:07-DQB1*05:03 may be because of lack of reactivity of available typing sera, or disruption of proper assembly of DQ heterodimer. The cDNA sequence of DQA1*01:07 is nearly identical to DQA1*01:04 except for a variant at position 304, which results in the replacement of an arginine with a cysteine at 79α. To determine whether the DQA1*01:07 product can be expressed on cell-surface, we co-expressed DQA1*01:07 with various DQB1*05 or *06 alleles in fibroblast cells. Cell-surface expression of DQ was detectable when DQA1*01:07 was co-expressed with DQB1*06:04 but undetectable with other DQB1*05 and DQB1*06 alleles, including DQB1*05:03, to which DQA1*01:07 was encoded in cis. These data suggest that DQA1*01:07 may act as a phenotypically null allele in the DQA1*01:07-DQB1*05:03 haplotype, while it can be expressed at a low level in the presences of certain DQB1*06 alleles, such as DQB1*06:04, in trans. Based on the null or low expression of DQA1*01:07 as shown in the previous and present studies, DQA1*01:07 has recently been renamed to DQA1*01:07Q, indicating its questionable expression.

Tmem2 Deficiency Leads to Enamel Hypoplasia and Soft Enamel in Mouse.

Teeth consist of 3 mineralized tissues: enamel, dentin, and cementum. Tooth malformation, the most common craniofacial anomaly, arises from complex genetic and environmental factors affecting enamel structure, size, shape, and tooth eruption. Hyaluronic acid (HA), a primary extracellular matrix component, contributes to structural and physiological functions in periodontal tissue. Transmembrane protein 2 (TMEM2), a novel cell surface hyaluronidase, has been shown to play a critical role during embryogenesis. In this study, we demonstrate Tmem2 messenger RNA expression in inner enamel epithelium and presecretory, secretory, and mature ameloblasts. Tmem2 knock-in reporter mice reveal TMEM2 protein localization at the apical and basal ends of secretory ameloblasts. Micro-computed tomography analysis of epithelial-specific Tmem2 conditional knockout (Tmem2-CKO) mice shows a significant reduction in enamel layer thickness and severe enamel deficiency. Enamel matrix protein expression was remarkably downregulated in Tmem2-CKO mice. Scanning electron microscopy of enamel from Tmem2-CKO mice revealed an irregular enamel prism structure, while the microhardness and density of enamel were significantly reduced, indicating impaired ameloblast differentiation and enamel matrix mineralization. Histological evaluation indicated weak adhesion between cells and the basement membrane in Tmem2-CKO mice. The reduced and irregular expressions of vinculin and integrin ß1 suggest that Tmem2 deficiency attenuated focal adhesion formation. In addition, abnormal HA accumulation in the ameloblast layer and weak claudin 1 immunoreactivity in Tmem2-CKO mice indicate impaired tight junction gate function. Irregular actin filament assembly was also observed at the apical and basal ends of secretory ameloblasts. Last, we demonstrated that Tmem2-deficient mHAT9d mouse ameloblasts exhibit defective adhesion to HA-containing substrates in vitro. Collectively, our data highlight the importance of TMEM2 in adhesion to HA-rich extracellular matrix, cell-to-cell adhesion, ameloblast differentiation, and enamel matrix mineralization.

Assessment of salivary gland dysfunction following chemoradiotherapy using quantitative salivary gland scintigraphy.

PURPOSE: To assess chemoradiotherapy-induced salivary gland dysfunction using quantitative salivary gland scintigraphy (QSGS), and whether QSGS is capable of predicting the grade of persistent salivary dysfunction after chemoradiotherapy. METHODS: From a time-activity curve using a stimulation test, the washout rate (WR) calculated was assessed. All glands (n = 155) were classified into four groups: a no-therapy group (n = 18), a chemotherapy alone group (n = 31), a radiotherapy alone group (n = 50), and a chemoradiotherapy group (n = 56). Subjective descriptions of xerostomia were recorded 1 year after the completion of the treatment period, and the 32 glands subjected to irradiation with or without chemotherapy were assessed. RESULTS: The WR values were significantly lower in glands that received chemoradiotherapy than in glands treated with radiotherapy alone (mean: 0.75 x 10(-3), n = 40 vs. 0.22, n = 36, p < 0.015), but there was no significant difference in the WR values between the no-therapy group and the chemotherapy alone group. The mean values of WR were lower in the chemoradiotherapy glands than in the radiotherapy alone glands in each of cumulative dose ranges of 1-20, 21-30, and 31-60 Gy. With regard to recovery from xerostomia, the WR values at a cumulative dose range of 20 to 40 Gy were significantly lower in the not improved group (-0.418, n = 16) than in the improved group (0.245, n = 16) (p < 0.0001). CONCLUSION: Chemotherapy per se has no or little adverse effect on salivary function, but combination chemotherapy can deteriorate radiation-induced injury of the salivary glands. QSGS appears useful in predicting the grade of persistent xerostomia following chemoradiotherapy.

A dual computed tomography linear accelerator unit for stereotactic radiation therapy: a new approach without cranially fixated stereotactic frames.

PURPOSE: To perform stereotactic radiation therapy (SRT) without cranially fixated stereotactic frames, we developed a dual computed tomography (CT) linear accelerator (linac) treatment unit. METHODS AND MATERIALS: This unit is composed of a linac, CT, and motorized table. The linac and CT are set up at opposite ends of the table, which is suitable for both machines. The gantry axis of the linac is coaxial with that of the CT scanner. Thus, the center of the target detected with the CT can be matched easily with the gantry axis of the linac by rotating the table. Positioning is confirmed with the CT for each treatment session. Positioning and treatment errors with this unit were examined by phantom studies. Between August and December 1994, 8 patients with 11 lesions of primary or metastatic brain tumors received SRT with this unit. All lesions were treated with 24 Gy in three fractions to 30 Gy in 10 fractions to the 80% isodose line, with or without conventional external beam radiation therapy. RESULTS: Phantom studies revealed that treatment errors with this unit were within 1 mm after careful positioning. The position was easily maintained using two tiny metallic balls as vertical and horizontal marks. Motion of patients was negligible using a conventional heat-flexible head mold and dental impression. The overall time for a multiple noncoplanar arcs treatment for a single isocenter was less than 1 h on the initial treatment day and usually less than 20 min on subsequent days. Treatment was outpatient-based and well tolerated with no acute toxicities. Satisfactory responses have been documented. CONCLUSION: Using this treatment unit, multiple fractionated SRT is performed easily and precisely without cranially fixated stereotactic frames.

Intrafractional tumor position stability during computed tomography (CT)-guided frameless stereotactic radiation therapy for lung or liver cancers with a fusion of CT and linear accelerator (FOCAL) unit.

PURPOSE: To evaluate intrafractional tumor position stability during computed tomography (CT)-guided frameless stereotactic radiation therapy (SRT) for lung or liver cancers, we checked repeated CT scanning, with a fusion of CT and linear accelerator (FOCAL) unit. METHODS AND MATERIALS: The FOCAL unit is a combination of a linear accelerator (Linac), CT scanner, X-ray simulator (X-S), and carbon table, and is designed to achieve CT-guided SRT with daily CT positioning followed by immediate irradiation while patients keep reduced shallow respirations. To evaluate intrafractional tumor position stability, 50 lung or liver lesions in 20 patients were checked by repeated CT scanning just before and after irradiation, and the obtained images were compared. RESULTS: There was no case with the intrafractional error judged to be greater than 10 mm. In 68% of cases, the intrafractional positioning errors were negligible (0-5 mm). CONCLUSIONS: Using the FOCAL unit, SRT for lung or liver cancers could be performed with intrafractional positioning errors not greater than 10 mm.

Computed tomography-guided frameless stereotactic radiotherapy for stage I non-small cell lung cancer: a 5-year experience.

PURPOSE: Stereotactic radiotherapy (SRT) is highly effective for brain metastases from non-small-cell lung cancers (NSCLCs). As such, primary lesions of NSCLC may also be treated effectively by similar focal high-dose SRT. METHODS AND MATERIALS: Between October 1994 and June 1999, 50 patients with pathologically proven T1-2N0 M0 NSCLC were treated by CT-guided frameless SRT. Of these, 21 patients were medically inoperable and the remainder were medically operable but refused surgery. In most patients, SRT was 50-60 Gy in 5-10 fractions for 1-2 weeks. Eighteen patients also received conventional radiotherapy of 40-60 Gy in 20-33 fractions before SRT. RESULTS: With a median follow-up period of 36 months (range 22-66), 30 patients were alive and disease free, 3 were alive with disease, 6 had died of disease, and 11 had died intercurrently. Local progression was not observed on follow-up CT scans in 47 (94%) of 50 patients. The 3-year overall survival rate was 66% in all 50 patients and 86% in the 29 medically operable patients. The 3-year cause-specific survival rate of all 50 patients was 88%. No definite adverse effects related to SRT were noted, except for 2 patients with a minor bone fracture and 6 patients with temporary pleural pain. CONCLUSIONS: SRT is a very safe and effective treatment for Stage I NSCLC. Additional studies involving a larger patient population and longer follow-up periods are warranted to assess this new treatment for early-stage lung cancer.

Does bone SPECT actually have lower sensitivity for detecting vertebral metastasis than MRI?

UNLABELLED: We compared the ability of bone SPECT and MRI to detect vertebral metastasis. METHODS: Skeletal scintigraphy, including planar and SPECT imaging, and spinal MRI examinations, were performed in 22 cancer patients in whom a total of 88 metastatic foci and 12 degenerative joint disease lesions were detected. Metastatic foci were defined as lesions that suggested metastasis on MRI and/or bone destruction on radiographs or CT and/or aggravation of increased tracer uptakes on serial bone scans. Image reconstruction of axial, coronal and sagittal sections was processed in a 128 X 128 matrix. MRI studies were performed with a 1.5 tesla signal scanner using fast spin-echo sequences. T1- and T2-weighted images were obtained in the sagittal plane. RESULTS: Twenty patients had at least one vertebral metastasis. MRI diagnosed 86 of the 88 (97.7%) metastatic foci; bone SPECT correctly diagnosed 81 of 88 (92.0%); and planar imaging detected 62 of 88 (70.4%). The two vertebrae with metastasis not detected by MRI were clearly seen by bone SPECT. Extra-vertebral body metastases (e.g. in the pedicle, lamina, transverse and spinous processes) were, however, most often detected by SPECT, followed by MRI and planar imaging (40 versus 32 versus 4). CONCLUSION: Vertebral SPECT, using high-resolution SPECT equipment, produced excellent results that were comparable to and complementary with MRI in detecting vertebral metastasis. Our data suggest that vertebral SPECT is superior to MRI in detecting extra-vertebral body metastasis.

Noninvasive visualization of coronary arterial aneurysm in infants and young children with mucocutaneous lymph node syndrome with two dimensional echocardiography.

Real time two dimensional echocardiographic studies of the main coronary arteries were performed in 30 normal subjects and 58 patients with the mucocutaneous lymph node syndrome. Four echocardiographic coronary arterial patterns were observed: linear, dilated, fusiform or spherical. In normal subjects the left main coronary artery generally had a linear pattern but had a dilated pattern in two patients. The right coronary artery could not be visualized clearly. In 7 of the 58 patients with the mucocutaneous lymph node syndrome, a portion of the left main coronary artery had a fusiform or spherical pattern, or both, and the stem of the right coronary artery also had a spherical pattern in 2 patients. In all five patients who had coronary angiography, the procedure confirmed an aneurysm in the left main coronary artery or its branching point and the stem of the left anterior descending coronary artery or the stem of the right coronary artery, or both. In three of the five patients, coronary arterial aneurysms were predicted before coronary angiography was performed. Thus, two dimensional echocardiography is a reliable noninvasive method for evaluating coronary arterial aneurysms in infants and young children.

Clinical course of cardiovascular involvement in the mucocutaneous lymph node syndrome. Relation between clinical signs of carditis and development of coronary arterial aneurysm.

Seventy-nine patients with mucocutaneous lymph node syndrome were evaluated prospectively by clinical examination, electrocardiography, chest radiography, M mode and two dimensional echocardiography and thallium-201 myocardial scanning. Serial changes were categorized according to the duration of illness: stage I (1 to 10 days), stage II (11 to 20 days), stage III (21 to 30 days), stage IV (31 to 60 days) and stage V (61 days to 40 months). The presence of myocarditis in stages I and II was suggested in 40 of 79 patients (50.6 percent) by electrocardiographic, echocardiographic, radiographic and clinical abnormalities. Myocarditis was accompanied by pericarditis in six patients and by both endocarditis and pericarditis in one patient. These signs of inflammation were resolved by stage III in all but three patients with electrocardiographic abnormalities. In the active stage, large coronary arterial lesions were suspected only because of an abnormal spherical echo-free space in the region of the coronary arteries on two dimensional echocardiograph as well as electrocardiographic evidence of deep Q waves in leads II, III and aVF. One or more coronary aneurysms developed in 11 patients, primarily in stage II; regression of the aneurysm was noted in 5 of these patients during stages III, IV and V. Aneurysm regression demonstrated by angiography did not correlate with echocardiographic changes in aneurysm size in one patient. Moreover, the occurrence of coronary aneurysm did not correlate with the presence of signs of carditis, because the frequency of carditis was the same in patients with and without aneurysm.

Daily positioning accuracy of frameless stereotactic radiation therapy with a fusion of computed tomography and linear accelerator (focal) unit: evaluation of z-axis with a z-marker.

To evaluate quantitative positioning errors of frameless stereotactic radiation therapy with a fusion of computed tomography (CT) and linear accelerator unit, Z-type CT markers were attached to patients, and CT images were obtained before and after daily treatment. In 40 verification tests, geometrical errors were never more than 1 mm.

Use of contrast-enhanced computed tomography to measure clearance per unit renal volume: a novel measurement of renal function and fractional vascular volume.

The iodinated contrast agents used for computed tomography (CT) have pharmacokinetics similar to inulin and can measure physiological indices, such as clearance per unit renal volume (alpha/V) and fractional vascular volume (fvv). Clinical experience with these techniques is, however, scanty, and the present study explored their potential in subjects with and without renal dysfunction. In a series of subjects, a single slice of kidney was scanned sequentially after the bolus injection of contrast material. Time-attenuation curves were constructed, and alpha/V and fvv were calculated using a Patlak graphic analysis. In the first part of the study, 50 normal kidneys in 35 subjects (aged 21 to 75 years) were studied. In the second stage, alpha/V was compared with glomerular filtration rate (GFR) measurements in 24 patients with diabetes (aged 28 to 84 years) with or without renal dysfunction. In normal kidneys, alpha/V averaged 0.49 +/- 0.11 mL/min/mL and fvv averaged 35% +/- 12%. These values agree with literature data obtained using other techniques. A negative correlation was seen between age and alpha/V (r = 0.66; P < 0.0001), but not fvv. In patients with diabetes, a strong correlation was observed between renal clearance values, calculated from CT and corrected for renal volume, and GFR (r = 0.87; P < 0.0001). Dynamic CT can provide quantitative renal physiological information on a regional basis noninvasively.

Decision-tree sensitivity analysis for cost-effectiveness of chest 2-fluoro-2-D-[(18)F]fluorodeoxyglucose positron emission tomography in patients with pulmonary nodules (non-small cell lung carcinoma) in Japan.

CONTEXT: Recent studies have demonstrated the potential cost-effectiveness of using 2-fluoro-2-D-[(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in the management of non-small cell lung carcinoma (NSCLC), but because of differences in health-care systems, those findings may not hold true in a Japanese hospital. OBJECTIVE: To assess the cost-effectiveness of the chest CT plus chest FDG-PET strategy in Japan. DESIGN: Decision-tree sensitivity analysis based on the two competing strategies of chest CT-alone vs chest CT plus chest FDG-PET. STUDY SELECTION: A simulation of 1,000 patients in whom NSCLC, stage IIIB or less, was suspected was created using baselines of other relevant variables in regard to sensitivity, specificity, mortality, life expectancy, and cost from published data. METHODS: We surveyed the relevant literature for the choice of variables. MAIN OUTCOME MEASURES: Expected marginal cost and expected life expectancy gain for NSCLC patients. RESULTS: The chest CT plus chest FDG-PET strategy yielded an expected life expectancy gain of 0.607 years (7.3 months) per patient, compared with the alternative strategy of chest CT-alone. Using an FDG-PET examination cost of 1.0 x 10(5) yen (around $700 US) per study, the cost increment was 2.18 x 10(5) yen/yr/patient. CONCLUSIONS: The chest CT plus chest FDG-PET strategy in patients with NSCLC is unlikely to be cost-effective in Japan. However, patient life expectancy gain would increase as a result of improved staging of NSCLC. These preliminary results should be confirmed by further studies for specific environments.

Usual interstitial pneumonia associated with primary Sjögren's syndrome.

We describe the first case, to our knowledge, of usual interstitial pneumonia (UIP) as the pulmonary manifestation in primary Sjögren's syndrome (SjS). A 45-year-old woman was admitted to our hospital because of a dry cough and an interstitial shadow on a chest roentgenogram. Labial biopsy and sialogram confirmed a diagnosis of SjS. BAL fluid analysis revealed lymphocytosis with a decreased CD4/CD8 ratio compatible with bronchiolitis obliterans organizing pneumonia or lymphoid interstitial pneumonia. Open-lung biopsy specimen, however, showed evidence of UIP. Open-lung biopsy was a useful and necessary examination to determine the nature of the pulmonary complication in primary SjS. Conservative treatment without corticosteroids maintained a stable condition for a follow-up period of 3 years.

Two-color analysis of lymphocyte subsets of bronchoalveolar lavage fluid and peripheral blood in Japanese patients with sarcoidosis.

Analysis of T-cell surface markers was carried out in peripheral blood and bronchoalveolar lavage (BAL) fluid of Japanese patients with sarcoidosis to examine the influence of differing racial background. The subjects were 26 untreated patients in whom a diagnosis of active sarcoidosis had recently been established and 9 healthy volunteers, and two-color immunofluorescence analysis was performed. CD3+HLA-DR+ cells, CD4+HLA-DR+ cells, and CD4+CD29+ cells in peripheral blood and BAL fluid were significantly increased in the patients compared with the healthy volunteers, and the mean percentages increased in parallel with the extent of the radiologic stage. The percentage of CD3+HLF-DR+ cells in peripheral blood and lavage fluid also significantly correlated with serum activity of angiotensin-converting enzyme (r = 0.69, p < 0.001; r = 0.61, p < 0.001, respectively). Thus, the evaluation of these antigens' expression is an important clinical approach for the staging of the disease. However, no significant differences were found in CD3+CD25+, CD4+CD45RA+, or CD8+CD11+ cells in either peripheral blood or BAL fluid between the patients and volunteers. Our results indicated that in Japanese patients with sarcoidosis, circulating T cells are activated but CD25+ cells are not increased in peripheral blood and BAL fluid, but there is not a significant association with racial background.

Ventricular fibrillation. A complication and hazard of transcatheter obliteration of the renal artery with absolute ethanol in dogs.

Selective renal artery embolization with absolute ethanol was performed without balloon occlusion in a series of 11 healthy mongrel dogs. Electrocardiogram, blood ethanol level, heart rate, and blood pressure of the aorta and pulmonary artery were monitored. Ventricular extrasystoles and/or ventricular fibrillation occurred in six of the 11 dogs, to which absolute ethanol in doses ranging from 0.09 to 0.40 ml/kg was administered. In three of these six animals, the electrocardiograms showed only ventricular extrasystoles after intra-arterial bolus injection of absolute ethanol at doses of less than 0.15 ml/kg and subsequent recovery to a normal sinus rhythm. Ventricular fibrillation subsequent to ventricular extrasystoles immediately after intra-arterial injection of absolute ethanol at doses of more than 0.18 ml/kg occurred in three. In five of eight dogs that survived after alcohol injection in this series, a severe hypertensive response was observed. Absolute ethanol has the potential hazard of causing ventricular arrhythmia. Thus, careful observations should be undertaken in clinical therapeutic application of this agent, particularly in the absence of balloon occlusion, absolute ethanol should never be used without monitoring the electrocardiogram.

Low-dose particulate polyvinylalcohol embolization in massive small artery intestinal hemorrhage. Experimental and clinical results.

The branches of the superior mesenteric artery were embolized with polyvinylalcohol (PVA) particles 149 to 250 mu (small), 420 to 590 mu (medium), and 590 to 1000 mu (large), respectively, in three groups of dogs. In the small PVA particle group, all three dogs died. In the medium and the large PVA particle groups, nine of the 11 dogs showed no significant ischemic change and the remaining two (one dog in the medium PVA group and one in the large PVA group) had a superficial ulcer. This study suggests that PVA embolization can be performed safely if particles of 420 mu or larger are used. In clinical studies, large PVA particles were used in embolization therapy for massive intestinal hemorrhage from small arteries in five patients. All had the hemorrhage from ulcer disease in the small bowel (four patients) and the ascending colon (one patient). Three patients were completely controlled with no recurrence of hemorrhage. The remaining two experienced rebleeding after embolization. No major complication was found in this series. It is concluded that low-dose large PVA particles are suitable as an embolic material for transcatheter occlusion of small-artery intestinal hemorrhage.

Growth-hormone-induced changes in postheparin plasma lipoprotein lipase and hepatic triglyceride lipase activities.

A comparison of treated and untreated patients with growth hormone deficiency revealed that administration of growth hormone reduced lipoprotein lipase and hepatic lipase activities, total cholesterol, and high-density lipoprotein cholesterol concentrations. The possible significance of these results is discussed.

Depressor effect of intraventricular administration of calcium on spontaneously hypertensive rats.

The role of central Ca2+ in the regulation of blood pressure (BP) was investigated in conscious spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY). Ten microliters of a high Ca2+ solution (Ca2+: 32.6 mM) administered intracerebroventricularly (i.c.v.) decreased the mean arterial pressure (MAP) for more than 20 min in SHR (n = 7, P < 0.005), while no change of MAP was observed in the WKY (n = 6). This depressor response to Ca2+ i.c.v. was dose-dependent at Ca2+ concentrations between 16.3 and 65.2 mM. We also investigated the effect of high Ca2+ i.c.v. in SHR after pretreatment with Ca2+ channel blockers, diltiazem (60 micrograms/10 microliters) or nisoldipine (4, 8, 16 and 32 micrograms/10 microliters), administered i.c.v., the autonomic ganglion blocker, hexamethonium (50 mg/kg), administered i.v. and alpha-methyl-p-tyrosine (100 and 400 micrograms/10 microliters) delivered i.c.v. Pretreatment with i.c.v. diltiazem (n = 8) or nisoldipine (n = 5 for 8 micrograms, n = 6 for 4, 16, 32 micrograms) abolished and/or blunted the decrease of MAP due to high Ca2+. Hexamethonium administered i.v. (n = 6) also canceled the depressor action of i.c.v. Ca2+. Pretreatment with 100 micrograms of i.c.v. alpha-methyl-p-tyrosine could not prevent the depressor action of i.c.v. Ca2+; however, 400 micrograms of alpha-methyl-p-tyrosine administered i.c.v. abolished the effect of i.c.v. Ca2+. Furthermore Ca2+ channel blockers administered i.c.v. in themselves increased MAP in SHR (P < 0.05). These results suggest that central Ca2+ is involved in the central regulation of BP in SHR. This effect may be mediated through changes in sympathetic activity.

Contribution of the central interaction between calcium and sodium to hemodynamic regulation in spontaneously hypertensive rats.

The contribution of the central interaction between calcium and sodium to hemodynamic regulation was assessed in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats. The effect of a high calcium solution (Ca2+, 130 mg/dl, 10 microliters) infused into the cerebral ventricle (i.c.v.) on hemodynamic responses induced by a high sodium solution (Na+, 1,000 mEq/1, 10 microliters) i.c.v. and the mechanism by which high Ca2+ affects the hemodynamic responses induced by high Na+ i.c.v. were studied. High Na+ i.c.v. induced a pressor response with tachycardia in the SHRs, but induced a pressor response with reflex bradycardia in the WKYs. Prior treatment with high Ca2+ i.c.v. attenuated the pressor response induced by high Na+ i.c.v. (+55.6 +/- 4.4 to +33.1 +/- 3.2 mmHg, P < 0.01) and restored reflex bradycardia (+86.4 +/- 7.7 to -26.7 +/- 7.6 bpm, P < 0.01) in SHRs. Whereas prior treatment with high Ca2+ i.c.v. attenuated the pressor response (+35.7 +/- 2.0 to +22.2 +/- 4.0 mmHg, P < 0.05), it did not alter the degree of reflex bradycardia (-81.7 +/- 7.1 to -69.2 +/- 120 bpm, n.s.) in WKYs. Ganglionic blockade attenuated the pressor response (+56.9 +/- 3.5 to +42.9 +/- 2.3 mmHg, P < 0.05) and restored reflex bradycardia (+82.1 +/- 10.3 to -65.9 +/- 11.0 bpm, P < 0.01) in SHRs, whereas, inhibition of arginine vasopressin attenuated the pressor response without modification of the tachycardic response.(ABSTRACT TRUNCATED AT 250 WORDS)