Coping strategies and risk of cardiovascular disease incidence and mortality: the Japan Public Health Center-based prospective Study.

AIMS: Coping strategies may be significantly associated with health outcomes. This is the first study to investigate the association between baseline coping strategies and cardiovascular disease (CVD) incidence and mortality in a general population cohort. METHODS AND RESULTS: The Japan Public Health Center-based prospective Study asked questions on coping in its third follow-up survey (2000-04). Analyses on CVD incidence and mortality included 57 017 subjects aged 50-79 without a history of CVD and who provided complete answers on approach- and avoidance-oriented coping behaviours and strategies. Cox regression models, adjusted for confounders, were used to determine hazard ratios (HRs) according to coping style. Mean follow-up time was 7.9 years for incidence and 8.0 years for mortality.The premorbid use of an approach-oriented coping strategy was inversely associated with incidence of stroke (HR = 0.85; 95% CI, 0.73-1.00) and CVD mortality (HR = 0.74; 95% CI, 0.55-0.99). Stroke subtype analyses revealed an inverse association between the approach-oriented coping strategy and incidence of ischaemic stroke (HR = 0.79; 95% CI, 0.64-0.98) and a positive association between the combined coping strategy and incidence of intra-parenchymal haemorrhage (HR = 2.03; 95% CI, 1.01-4.10). Utilizing an avoidance coping strategy was associated with increased mortality from ischaemic heart disease (IHD) only in hypertensive individuals (HR = 3.46; 95% CI, 1.07-11.18). The coping behaviours fantasizing and positive reappraisal were associated with increased risk of CVD incidence (HR = 1.24; 95% CI, 1.03-1.50) and reduced risk of IHD mortality (HR = 0.63; 95% CI, 0.40-0.99), respectively. CONCLUSION: An approach-oriented coping strategy, i.e. proactively dealing with sources of stress, may be associated with significantly reduced stroke incidence and CVD mortality in a Japanese population-based cohort.

Sudden onset of sleep due to hypothalamic lesions in neuromyelitis optica spectrum disorder positive for anti-aquaporin-4 antibody.

We report a patient with neuromyelitis optica spectrum disorders who presented with sudden onset of sleep as the sole manifestation. Magnetic resonance imaging investigation revealed lesions in the hypothalamus bilaterally, which vanished completely after methylprednisolone pulse therapy.

Characterization of ion-irradiated poly-L-lactic acid using nano-cutting.

Effects on the mechanical strength of poly-L-lactic acid (PLLA) upon irradiation with 150 keV He(+) ion were studied. Changes in the irradiated surface were investigated using a surface texture and contour measuring instrument and an atomic force microscope. Observations made with the atomic force microscope revealed that the irradiated surface subsided significantly as the fluence increased. In order to investigate the dependence on fluence of the depth of the Bragg peak for the ion implantation, the cutting strength, Σ, was analysed [F. Saito, I. Nishiyama and T. Hyodo, Mater. Lett., 2012, 66, 144-146]; this value is an indicator of the strength of a material against cutting, and is obtained from the cutting resistance. The averaged ion projected range increased from about 1.1 µm for a fluence of 1 × 10(15) He(+)/cm(2) to about 4 µm for a fluence of 1 × 10(16) He(+)/cm(2). The density of the region following irradiation was estimated using a combination of cutting resistance measurements and positron annihilation γ ray Doppler broadening measurements made with an energy-variable positron beam. The density decreased from the value of 1.27 g cm(-3) to about 0.6 g cm(-3) after irradiation with a fluence of 3 × 10(15) He(+)/cm(2). By considering the decrease in the density and the subsidence of the surface, it is concluded that only 30% of the original weight remained in the irradiated region after exposure to the He(+) ions. Anisotropic change in the cutting resistance suggests that mechanical strength in the direction normal to the surface increased while that in the lateral direction decreased.

Histological study of the nasal septal cartilage in BALB/c-bm/bm mouse which spontaneously induces malocclusion.

OBJECTIVES: The BALB/c-bm/bm mouse is characterized by short limbs and short tail attributed to undersulfated glycosaminoglycans. Anterior transverse crossbite sometimes spontaneously appears in BALB/c-bm/bm mice. The BALB/c-bm/bm mouse shows a short nose and cranium. The reason for hypo-growth of anterior craniofacial structures has not been clarified, although the nasal septal cartilage might be related to the growth of anterior craniofacial structures. Therefore, the purpose of this study was to evaluate histological findings of the nasal septal cartilage at the border region of the ethmoid and sphenoid bone in BALB/c-bm/bm mice. MATERIALS AND METHODS: BALB/c mice (wild type) and BALB/c-bm/bm mice with normal occlusion (bm/bm) were used. Sagittal sections of female mice aged 2, 4, and 8 weeks were stained with hematoxylin and eosin for histological analysis. RESULTS: At the border region between the nasal septal cartilage and the ethmoid bone in bm/bm, the area of proliferative zone was significantly smaller than that in wild type. At the border regions between the nasal septal cartilage and both the ethmoid and sphenoid bones, the number of proliferative chondrocytes was significantly smaller. Normal endochondral ossification was not observed at the border region between the nasal septal cartilage and the sphenoid bone in bm/bm. CONCLUSION: The findings suggest that disorder of endochondral ossification in the nasal septal cartilage contributes to the hypo-growth of anterior craniofacial structures in bm/bm.

Cumulative ecological impacts of two successive annual treatments of imidacloprid and fipronil on aquatic communities of paddy mesocosms.

Agricultural landscapes, including paddies, play an important role in maintaining biodiversity, but this biodiversity has been under the threat of toxic agro-chemicals. Our knowledge about how aquatic communities react to, and recover from, pesticides, particularly in relation to their residues, is deficient, despite the importance of such information for realistic environmental impact assessment of pesticides. The cumulative ecological impacts on aquatic paddy communities and their recovery processes after two successive annual applications of two systemic insecticides, imidacloprid and fipronil, were monitored between mid-May and mid-September each year. The abundance of benthic organisms during both years was significantly lower in both insecticide-treated fields than in the controls. Large-impacts of fipronil on aquatic arthropods were found after the two years. Growth of medaka fish, both adults and their juveniles, was affected by the application of the two insecticides. A Principal Response Curve analysis (PRC) showed the escalation and prolongation of changes in aquatic community composition by the successive annual treatments of each insecticide over two years. Residues of fipronil in soil, which are more persistent than those of imidacloprid, had a high level of impact on aquatic communities over time. For some taxonomic groups, particularly for water surface-dwelling and water-borne arthropods, the second annual treatment had far greater impacts than the initial treatment, indicating that impacts of these insecticides under normal use patterns cannot be accurately assessed during short-term monitoring studies, i.e., lasting less than one year. It is concluded that realistic prediction and assessment of pesticide effects at the community level should also include the long-term ecological risks of their residues whenever these persist in paddies over a year.

Morphological evaluation of cranial and maxillary shape differences of the brachymorphic mouse with spontaneous malocclusion using three-dimensional micro-computed tomography.

OBJECTIVES: The aim of this study was to determine whether significant cranial and maxillary deformity exists in BALB/c-bm/bm (brachymorphism) mouse with spontaneous malocclusion using three-dimensional (3D) images. MATERIALS AND METHODS: Thirty female mice were divided into the following three groups: control group (BALB/c mice, n = 10), Norm group (BALB/c-bm/bm mice with normal occlusion, n = 10), and Mal group (BALB/c-bm/bm mice with malocclusion, n = 10). Nine points in the skull were selected, and transverse and antero-posterior distances were measured using three-dimensional images of micro-computed tomography (CT). Moreover, 3D images were superimposed at the median plane to visualize the skull shape asymmetry. RESULTS: The transverse distances at the posterior cranial and maxillary region and the antero-posterior distances in the Norm and Mal groups were significantly shorter than those in the control group. The nasal septum of the Mal group was significantly shorter than that of the Norm group. Morphological measurements and superimposed 3D images showed that lateral deviation occurred at the anterior cranial and maxillary region in the Mal group. CONCLUSION: The 3D micro-CT images revealed that the antero-posterior length and posterior transverse width at the cranium and maxilla in BALB/c-bm/bm mice were significantly smaller than those in BALB/c mice. It was quantitatively and morphologically clear that BALB/c-bm/bm mice show a spontaneous transverse crossbite owing to lateral deviation of the maxilla and nasal bone.

A stoichiometric complex of neurexins and dystroglycan in brain.

In nonneuronal cells, the cell surface protein dystroglycan links the intracellular cytoskeleton (via dystrophin or utrophin) to the extracellular matrix (via laminin, agrin, or perlecan). Impairment of this linkage is instrumental in the pathogenesis of muscular dystrophies. In brain, dystroglycan and dystrophin are expressed on neurons and astrocytes, and some muscular dystrophies cause cognitive dysfunction; however, no extracellular binding partner for neuronal dystroglycan is known. Regular components of the extracellular matrix, such as laminin, agrin, and perlecan, are not abundant in brain except in the perivascular space that is contacted by astrocytes but not by neurons, suggesting that other ligands for neuronal dystroglycan must exist. We have now identified alpha- and beta-neurexins, polymorphic neuron-specific cell surface proteins, as neuronal dystroglycan receptors. The extracellular sequences of alpha- and beta-neurexins are largely composed of laminin-neurexin-sex hormone-binding globulin (LNS)/laminin G domains, which are also found in laminin, agrin, and perlecan, that are dystroglycan ligands. Dystroglycan binds specifically to a subset of the LNS domains of neurexins in a tight interaction that requires glycosylation of dystroglycan and is regulated by alternative splicing of neurexins. Neurexins are receptors for the excitatory neurotoxin alpha-latrotoxin; this toxin competes with dystroglycan for binding, suggesting overlapping binding sites on neurexins for dystroglycan and alpha-latrotoxin. Our data indicate that dystroglycan is a physiological ligand for neurexins and that neurexins' tightly regulated interaction could mediate cell adhesion between brain cells.

Twisted ovarian tumor causing progressive hemothorax: a case report of porous diaphragm syndrome.

BACKGROUND: Porous diaphragm syndrome is caused by a defect in the diaphragm. The defect may induce pleural effusion in a patient with an ovarian tumor. CASE REPORT: A 59-year-old Japanese woman with an ovarian tumor and right hemothorax underwent thoracotomy and presented with a fenestra in the right diaphragm through which bloody fluids were flowing from the peritoneal cavity into the pleural space. Following suturing of the fenestra, laparotomy revealed intraabdominal bleeding due to torsion of an ovarian tumor. CONCLUSION: This is the first report in which the diaphragmatic defect was identified in a patient with an ovarian tumor and hemothorax. Porous diaphragm syndrome may be involved in the pathophysiology of right pleural effusion observed in other medical conditions such as Meigs' syndrome, ovarian hyperstimulated syndrome, and ovarian cancer.

Simultaneous treatment of PVC and oyster-shell wastes by mechanochemical means.

This work presents a new process for dechlorinating poly-vinyl chloride (PVC) by the use of oyster-shell waste. The process consists of milling of PVC waste with oyster-shell waste, followed by washing the milled sample with water. The milling of PVC and oyster-shell mixture results in size reduction and rupture in bonds, leading to mechanically induced reactions between the two to form CaCl2 and hydrocarbon with C=C bonds. Washing the milled mixtures with water at room temperature allows complete removal of chlorine from the milled sample. More than 95% of chlorine in PVC was removed when 2h grinding is conducted for the mixture. The present process could offer a potential route to the handling and disposal of oyster-shell and PVC wastes.

Insulin attenuates agonist-mediated calcium mobilization in cultured rat vascular smooth muscle cells.

Insulin has been shown to attenuate pressor-induced vascular contraction, but the mechanism for this vasodilatory action is unknown. This study examines the effect of insulin on angiotensin II (ANG II)-induced increments in cytosolic calcium in cultured rat vascular smooth muscle cells (VSMC). 20-min incubations with insulin (10 microU/ml to 100 mU/ml) did not alter basal intracellular calcium concentration ([Ca2+]i), but inhibited the response to 100 nM ANG II in a dose-dependent manner (ANG II alone, 721 +/- 54 vs. ANG II + 100 mU/ml insulin, 315 +/- 35 nM, P < 0.01). A similar effect of insulin on ANG II action was observed in calcium poor buffer. Moreover, insulin did not effect calcium influx. ANG II receptor density and affinity were not affected by 24-h incubation with insulin. To further clarify the mechanisms of these observations, we measured ANG II-induced production of inositol 1,4,5-triphosphate (IP3), and IP3-releasable 45Ca. Insulin treatment did not alter ANG II-stimulated IP3 production. However, IP3-stimulated release of 45Ca in digitonin permeabilized cells was significantly reduced after 5-min incubations with 100 mU/ml insulin. Thapsigargin induced release of calcium stores was also blocked by insulin. Thus, insulin attenuates ANG II-stimulated [Ca2+]i primarily by altering IP3-releasable calcium stores. Insulin effects on ANG II-induced [Ca2+]i were mimicked by preincubation of VSMC with either sodium nitroprusside or 8-bromo-cGMP. As elevations in cGMP in vascular tissue lower [Ca2+]i, it is possible that insulin affects IP3 release of calcium by a cGMP-dependent mechanism that would contribute to its vasodilatory effects.

Cloning, characterization, and chromosomal mapping of human aquaporin of collecting duct.

We recently cloned a cDNA of the collecting duct apical membrane water channel of rat kidney, which is important for the formation of concentrated urine (Fushima, K., S. Uchida, Y. Hara, Y. Hirata, F. Marumo, and S. Sasaki. 1993. Nature [Lond.]. 361:549-552). Since urine concentrating ability varies among mammalian species, we examined whether an homologous protein is present in human kidney. By screening a human kidney cDNA library, we isolated a cDNA clone, designated human aquaporin of collecting duct (hAQP-CD), that encodes a 271-amino acid protein with 91% identity to rat AQP-CD. mRNA expression of hAQP-CD was predominant in the kidney medulla compared with the cortex, immunohistochemical staining of hAQP-CD was observed only in the collecting duct cells, and the staining was dominant in the apical domain. Functional expression study in Xenopus oocytes confirmed that hAQP-CD worked as a water channel. Western blot analysis of human kidney medulla indicated that the molecular mass of hAQP-CD is 29 kD, which is the same mass expected from the amino acid sequence. Chromosomal mapping of the hAQP-CD gene assigned its location to chromosome 12q13. These results could be important for future studies of the pathophysiology of human urinary concentration mechanisms in normal and abnormal states.

NFATx, a novel member of the nuclear factor of activated T cells family that is expressed predominantly in the thymus.

The nuclear factor of activated T cells (NFAT) regulates cytokine gene expression in T cells through cis-acting elements located in the promoters of cytokine genes. Here, we report the cDNA cloning, chromosomal localization, and initial characterization of a transcription factor related to NFATp and NFATc. The novel molecule, designated NFATx, exhibits in its middle a region very similar to the Rel homology domain in NFATc and NFATp. The amino-terminal region of NFATx also shows significant similarities to corresponding sequences in NFATc and NFATp and contains three copies of a conspicuous 17-residue motif of unknown function. We provide evidence showing that NFATx can reconstitute binding to the NFAT-binding site from the interleukin 2 promoter when combined with AP1 (c-Fos/c-Jun) polypeptides and that NFATx is capable of activating transcription of the interleukin 2 promoter in COS-7 cells when stimulated with phorbol ester and calcium ionophore. NFATx mRNA is preferentially and remarkably found in the thymus and at lower levels in peripheral blood leukocytes. The expression pattern of NFATx, together with its functional activity, strongly suggests that NFATx plays a role in the regulation of gene expression in T cells and immature thymocytes.

Return to home early days after acute aortic dissection surgery.

AIM: The length of hospital stay after acute aortic dissection surgery tends to be prolonged. The aim of this study is to assess the feasibility of our protocol for early discharge after acute aortic dissection surgery. METHODS: This study enrolled 17 consecutive acute aortic dissection patients who returned to their own home within 2 weeks of surgery. In seven patients total aortic arch replacement was performed and in 7 partial arch replacement. The main aim of the first 24 h after surgery was to achieve early extubation. Patients were encouraged to return to their own home 4 days and later after surgery. The prerequisite criteria for discharge were the following: independent mobility, stable hemodynamics, apyrexia, adequate oral intake, normal bowel function, healthy surgical wound and the patient's agreement for discharge. RESULTS: The mean age of these patients was 59. The postoperative ventilation time, length of intensive care unit stay and postoperative hospital stay were 11 h, 37 h and 6.9 days, respectively. Two (12%), 13 (76%) and 14 (82%) patients returned to their own home by postoperative day 4, 7 and 10, respectively. Three patients were readmitted to a peripheral hospital in the 4 week postoperative period. The reason for all readmissions was lack of family support. Two other patients underwent pericardiocentesis for pericardial effusion at an other hospital as outpatients. There was no complication caused by early discharge. CONCLUSIONS: Early discharge after aortic dissection surgery is safe and recommended to patients who have normal bowel function and adequate family support.

Differential expression of two BMP antagonists, gremlin and Follistatin, during development of the chick feather bud.

Expression of four BMP antagonist genes, noggin, chordin, gremlin and Follistatin, was examined during chick feather development. Although expression of noggin and chordin was not detected, gremlin and Follistatin were expressed differentially in feather buds. The differential expression patterns of gremlin and Follistatin change dynamically from the nascent inter-feather bud region to the posterior domain of the feather bud.

Potential role of 12 hydroxyeicosatetraenoic acid in angiotensin II-induced calcium signal in rat glomerulosa cells.

Recent evidence suggests that 12 hydroxyeicosatetraenoic acid (12HETE), a product of the 12 lipoxygenase (LO) pathway of arachidonic acid metabolism, may have a role in mediating angiotensin II (AII)-induced aldosterone secretion. The present study examined the possible role of the 12 LO product 12HETE in AII-induced calcium ([Ca++]i) signals in rat glomerulosa cells. The addition of 12HETE to glomerulosa cells induced a dose-dependent (10(-6)-10(-8) M) rise in [Ca++]i levels that was sustained over 15 min. The effects of 12HETE on [Ca++]i were attenuated but not blocked by nifedipine (5 x 10(-6) M) and were preserved in a calcium-free medium, suggesting mobilization of intracellular calcium stores. Furthermore, the 12HETE-mediated rise in [Ca++]i was almost entirely abolished by dantrolene. In parallel, 12HETE reversed the inhibitory effect of nifedipine on AII-induced aldosterone secretion [AII (10(-9) M) - 36 +/- 7, AII + nifedipine (5 x 10(-6) M) - 13 +/- 2, AII + nifedipine + 12HETE (5 x 10(-8) M) - 27 +/- 4 ng/10(6) cells]. Dantrolene also inhibited AII-dependent aldosterone secretion (AII 10(-9) M - 75.8 +/- 5.6, AII + dantrolene 10(-6) M 45.5 +/- 8.8 ng/10(-6) cells), but this inhibition could not be reversed by 12HETE 10(-8) M (45.4 +/- 10.6 ng/10(6) cells). The LO blockers baicalein and BW755C inhibited the effect of AII on aldosterone production and on [Ca++]i in a parallel fashion. During LO blockade, the addition of 12HETE (10(-7) M) restored the AII-induced rise in [Ca++]i. Collectively, these observations suggest that activation of the LO pathway in the rat adrenal glomerulosa contributes to change in cytosolic calcium, which may be important for the steroidogenic effect of AII.

Antihypertensive mechanism of diuretics based on pressure-natriuresis relationship.

We analyzed the hypotensive mechanisms of a thiazide-type diuretic, mefruside, on the basis of the pressure-natriuresis relationship. We performed a 5-week study in eight patients with essential hypertension who were given a high sodium diet (15 to 18 g NaCl per day) during the 1st and 5th weeks, a severely sodium-restricted diet (1 to 3 g/d) during the 2nd week, and a mildly sodium-restricted diet (5 to 7 g/d) during the 3rd and 4th weeks. Mefruside (25 mg/d) was administered during the 4th and 5th weeks. Urinary sodium excretion rate and mean arterial pressure were measured at the end of each week, and the pressure-natriuresis relationship was drawn by plotting urinary sodium excretion rate on the ordinate and mean arterial pressure on the abscissa before and after mefruside treatment. Before treatment, the pressure-natriuresis relationship was linear, and mean arterial pressure was changed as a consequence of sodium intake alteration (1st week, 117 +/- 9 mm Hg; 2nd week, 105 +/- 7; 3rd week, 109 +/- 9). After treatment, however, the change in mean arterial pressure was very small (4th week, 102 +/- 8 mm Hg; 5th week, 104 +/- 7). Mefruside steepened the slope of the relationship (20.8 +/- 10.5 versus 143 +/- 85 [mmol/d]/mm Hg, P <.005) without significantly shifting the x intercept (104 +/- 6 versus 101 +/- 9 mm Hg, P=NS) of the relationship. The increase in the slope was greater in patients whose slope had been depressed and blood pressure was sodium sensitive before mefruside treatment. The hypotensive effect of mefruside during a high sodium diet correlated positively with both the hypotensive effect of sodium restriction (r=.84, P <.01) and the increase in the slope by mefruside (r=.83, P <.02). Thus, mefruside lowers blood pressure especially in patients with high sodium sensitivity mainly by making blood pressure sodium insensitive through its diuretic action. Strict sodium restriction seems unnecessary when diuretics are administered for blood pressure control.

12-Lipoxygenase products modulate calcium signals in vascular smooth muscle cells.

Previous studies have shown that inhibition of the lipoxygenase pathway of arachidonic acid metabolism can prevent the development of elevated blood pressure in renin-dependent models of hypertension. Agents that inhibit the lipoxygenase pathway such as phenidone and the flavonoid baicalein can selectively attenuate contractile responses to angiotensin II in vivo as well as in isolated vascular tissue. In the present study, the effects of lipoxygenase inhibitors on pressor-induced changes in cytosolic calcium were examined in cultured rat vascular smooth muscle cells using the fluorescent dye fura-2. Two structurally unrelated lipoxygenase inhibitors, baicalein and 5,8,11-eicosatriynoic acid, attenuated angiotensin II-stimulated increases in cytosolic calcium in both normal and calcium-poor buffer. The addition of 5-, 12-, or 15(S)-hydroxyeicosatetraenoic acid alone to the cells had no acute effect on intracellular calcium concentration. However, the addition of 12(S)-hydroxyeicosatetraenoic acid but not 5- or 15(S)-hydroxyeicosatetraenoic acid restored the initial calcium response to angiotensin II in vascular smooth muscle cells pretreated with both inhibitors; 5,8,11-eicosatriynoic acid also reduced [Arg8]-vasopressin and endothelin-stimulated increases in intracellular calcium. The attenuation of vasopressor-induced calcium transients by agents that inhibit lipoxygenase may explain their observed hypotensive effects in vivo. Moreover, lipoxygenase products, in particular 12(S)-hydroxyeicosatetraenoic acid, may act as mediators for the intracellular actions of angiotensin II and possibly other pressor hormones in vascular tissue by regulation of intracellular calcium metabolism.

Kinins contribute to the improvement of insulin sensitivity during treatment with angiotensin converting enzyme inhibitor.

Although angiotensin converting enzyme inhibitors and alpha 1-blockers have been reported to improve insulin sensitivity, their mechanisms of action have not been elucidated. To investigate the role of kinins in insulin sensitivity, we treated 4-week-old spontaneously hypertensive rats with either an angiotensin converting enzyme inhibitor (enalapril), an alpha 1-blocker (doxazosin), or an angiotensin II antagonist (losartan) for 3 weeks. A control group received no drugs. In addition, 18 rats treated with enalapril or doxazosin received a simultaneous administration of a kinin antagonist (Hoe 140). Glucose clamp testing was performed in each group. Enalapril (128 +/- 1 mmHg) and doxazosin (132 +/- 2 mmHg) decreased mean blood pressure compared with control levels (148 +/- 1 mmHg) (P < .01). The glucose requirement for the clamp test during the administration of enalapril (25.8 +/- 0.5 mg/kg per minute) or doxazosin (28.6 +/- 0.7 mg/kg per minute) was higher than that of the control group (19.8 +/- 0.5 mg/kg per minute) (P < .05). Although Hoe 140 did not alter the glucose requirement of doxazosin (27.8 +/- 0.5 mg/kg per minute), it decreased that of enalapril (22.6 +/- 0.9 mg/kg per minute) (P < .05) without affecting the changes in mean blood pressure induced by enalapril. In addition, losartan decreased mean blood pressure but did not affect the glucose requirement. Thus, the improvement in insulin sensitivity produced by an angiotensin converting enzyme inhibitor is mostly dependent on kinins but not on angiotensin II antagonism, and an alpha 1-blocker improves insulin sensitivity irrespective of kinins.

Blood pressure response to hyperinsulinemia in salt-sensitive and salt-resistant rats.

We investigated the role of insulin in salt-sensitive hypertension in Dahl salt-sensitive and salt-resistant rats. The rats were kept in metabolic cages, and sodium intake and urinary sodium excretion were measured. In salt-sensitive rats receiving a 0.3% NaCl diet, sodium retention was significantly greater at weeks 1 and 2 in rats that received an insulin infusion than in those receiving a saline infusion. Mean arterial blood pressure and plasma norepinephrine levels were significantly higher at week 3 in insulin-treated rats than in saline-treated rats (mean arterial pressure, 137 +/- 3 mm Hg versus 119 +/- 3 mm Hg, p < 0.05; plasma norepinephrine, 0.40 +/- 0.02 ng/ml versus 0.27 +/- 0.01 ng/ml, p < 0.05). Insulin did not influence sodium retention, mean arterial pressure, or plasma norepinephrine in salt-resistant rats. Coadministration of an alpha-blocker (bunazosin, 10 mg/kg per day for 3 weeks) in salt-sensitive rats abolished the insulin-induced elevations in mean arterial pressure and sodium retention. When salt-sensitive rats were fed a low salt diet (0.03% NaCl), insulin did not raise mean arterial pressure. Thus, insulin elevated blood pressure only in the salt-sensitive model. The sympathetic nervous system and sodium retention in the early phase of insulin overload may contribute to elevation of mean arterial pressure in this model.