Chronic activation of neurokinin-1 receptor induces pulmonary hypertension in rats. (1/437)

In this study we explored the hypothesis that chronic activation of neurokinin-1 (NK-1) receptor induces pulmonary hypertension in Wistar rats. First, the activation of NK-1 receptor on the pulmonary circulation was investigated by use of a chronic injection of NK-1 agonist [Ser9,Met(O2)11]-substance P (1 x 10(-9) mol/kg) for 2 wk at sea level (rats breathed room air) and during hypoxia (rats were placed in a hypobaric 380-Torr chamber). Second, we studied the effect of NK-1 antagonist (CP-96345) on developing and developed (after 4 wk of chronic hypoxia) pulmonary hypertension. Pulmonary arterial pressure, the weight ratio of right ventricle to left ventricle + septum, hematocrit, and substance P (SP) were measured. We found that NK-1 agonist significantly increased pulmonary arterial pressure in the sea-level but not in the hypoxic group. However, NK-1 agonist induced neither right heart hypertrophy nor polycythemia. CP-96345 significantly decreased pulmonary arterial pressure in the hypoxic group but had no effect in the sea-level group. Furthermore, CP-96345 significantly attenuated the acute SP-induced increase in pulmonary arterial pressure in the sea-level and hypoxic groups, with a larger increase in the hypoxic group. These results suggest that chronic activation of NK-1 receptor induces pulmonary hypertension and that there is an increase in the sensitivity of pulmonary vessels in response to SP in chronically hypoxic rats.  (+info)

Particulate air pollution and daily mortality on Utah's Wasatch Front. (2/437)

Reviews of daily time-series mortality studies from many cities throughout the world suggest that daily mortality counts are associated with short-term changes in particulate matter (PM) air pollution. One U.S. city, however, with conspicuously weak PM-mortality associations was Salt Lake City, Utah; however, relatively robust PM-mortality associations have been observed in a neighboring metropolitan area (Provo/Orem, Utah). The present study explored this apparent discrepancy by collecting, comparing, and analyzing mortality, pollution, and weather data for all three metropolitan areas on Utah's Wasatch Front region of the Wasatch Mountain Range (Ogden, Salt Lake City, and Provo/Orem) for approximately 10 years (1985-1995). Generalized additive Poisson regression models were used to estimate PM-mortality associations while controlling for seasonality, temperature, humidity, and barometric pressure. Salt Lake City experienced substantially more episodes of high PM that were dominated by windblown dust. When the data were screened to exclude obvious windblown dust episodes and when PM data from multiple monitors were used to construct an estimate of mean exposure for the area, comparable PM-mortality effects were estimated. After screening and by using constructed mean PM [less than/equal to] 10 microm in aerodynamic diameter (PM10) data, the estimated percent change in mortality associated with a 10-mg/m3 increase in PM10 (and 95% confidence intervals) for the three Wasatch Front metropolitan areas equaled approximately 1. 6% (0.3-2.9), 0.8% (0.3-1.3), and 1.0% (0.2-1.8) for the Ogden, Salt Lake City, and Provo/Orem areas, respectively. We conclude that stagnant air pollution episodes with higher concentrations of primary and secondary combustion-source particles were more associated with elevated mortality than windblown dust episodes with relatively higher concentrations of coarse crustal-derived particles.  (+info)

Unhealthy effects of atmospheric temperature and pressure on the occurrence of myocardial infarction and coronary deaths. A 10-year survey: the Lille-World Health Organization MONICA project (Monitoring trends and determinants in cardiovascular disease). (3/437)

BACKGROUND: Associations between an increase in coronary heart disease occurrence and low atmospheric temperatures have been reported from mortality data and hospital admission registries. However, concomitant increases in noncardiovascular case fatality rates and selection bias of hospital cases may weaken this observation. In this study, we addressed the question of the relationships between fatal and nonfatal coronary diseases and meteorological variables in 10-year data (1985 to 1994) collected in a morbidity registry (Lille-WHO MONICA Project) monitoring 257 000 men from 25 to 64 years of age. METHODS AND RESULTS: The impacts of atmospheric temperature (in Celsius) and pressure (in millibars) on daily rates of myocardial infarction (MI) and coronary deaths were studied. Percentages of variation of event rates according to meteorological variations were derived from the relative risks estimated with a Poisson regression model. During the 10-year longitudinal survey, 3616 events occurred. Rates of events decreased linearly with increasing atmospheric temperature. For atmospheric pressure, we detected a V-shaped relationship, with a minimum of daily event rates at 1016 mbar. A 10 degrees C decrease was associated with a 13% increase in event rates (P<0.0001); a 10-mbar decrease <1016 mbar and a 10-mbar increase >1016 mbar were associated with a 12% increase (P=0.001) and an 11% increase (P=0. 01) in event rates, respectively. These effects were independent and influenced both coronary morbidity and mortality rates, with stronger effects in older age groups and for recurrent events. CONCLUSIONS: This longitudinal study is the first to estimate the attributable effect of meteorological variables on MI morbidity in population and strongly argues for a systematic fight against cold in cardiovascular disease prevention, particularly in older ages and after a first MI.  (+info)

Changes in c-Fos expression induced by noxious stimulation in the trigeminal spinal nucleus caudalis and C1 spinal neurons of rats after hyperbaric exposure. (4/437)

The present study aims to test the hypothesis that hyperbaric exposure inhibits nociceptive processing in the trigeminal spinal nucleus caudalis and C1 spinal neurons. We investigated the c-Fos-like immunoreactivity of the brainstem and upper cervical spinal cord (C1 region) following an injection of mustard oil (15 microliters of 20%) into the nasal mucosa of pentobarbital anesthetized rats after exposure to hyperbaric (2-atmospheres, 1 h) and normobaric pressures. After the hyperbaric exposure, the mean number of Fos-immunoreactive neurons in the ipsilateral laminae I-II and III-IV of the trigeminal spinal nucleus caudalis were significantly lower than those in the normobaric condition. Similarly, the mean number of c-Fos positive neurons in the superficial layer (I-II) of the ipsilateral C1 segment were significantly reduced as compared with that in the normobaric condition. When treated with the vehicle alone, no significant difference was detected in the numbers of c-Fos positive neurons in the trigeminal spinal nucleus caudalis and C1 regions between hyperbaric and normobaric conditions. These results suggest that hyperbaric exposure may attenuate nociceptive signals from the area innervated by the trigeminal nerves at the level of both the trigeminal spinal nucleus caudalis and C1 dorsal horn.  (+info)

Tissue factor activity is increased in human endothelial cells cultured under elevated static pressure. (5/437)

We tested the hypothesis that elevated blood pressure, a known stimulus for vascular remodeling and an independent risk factor for the development of atherosclerotic disease, can modulate basal and cytokine-induced tissue factor (TF; CD 142) expression in cultured human endothelial cells (EC). Using a chromogenic enzymatic assay, we measured basal and tumor necrosis factor-alpha (TNF-alpha; 10 ng/ml, 5 h)-induced TF activities in human aortic EC (HAEC) and vena cava EC (HVCEC) cultured at atmospheric pressure and at 170 mmHg imposed pressure for up to 48 h. Basal TF activities were 22 +/- 10 U/mg protein for HAEC and 14 +/- 9 U/mg protein for HVCEC and were upregulated in both cell types >10-fold by TNF-alpha. Exposure to pressure for 5 h induced additional elevation of basal TF activity by 47 +/- 16% (P < 0.05, n = 6) for HAEC and 17 +/- 5% (P < 0.05, n = 3) for HVCEC. Pressurization also enhanced TF activity in TNF-alpha-treated cells from 240 +/- 28 to 319 +/- 32 U/mg protein in HAEC (P < 0.05, n = 4) and from 148 +/- 25 to 179 +/- 0.8 U/mg protein (P < 0.05, n = 3) in HVCEC. Cytokine stimulation caused an approximately 100-fold increase in steady-state TF mRNA levels in HAEC, whereas pressurization did not alter either TF mRNA or cell surface antigen expression, as determined by quantitative RT-PCR methodology and ELISA. Elevated pressure, however, modulated the EC plasma membrane organization and/or permeability as inferred from the increased cellular uptake of the fluorescent amphipathic dye merocyanine 540 (33 +/- 7%, P < 0.05). Our data suggest that elevated static pressure modulates the hemostatic potential of vascular cells by modifying the molecular organization of the plasma membrane.  (+info)

Influence of environmental temperature on incidence of indinavir-related nephrolithiasis. (6/437)

We analyzed the influence of temperature, humidity, and atmospheric pressure on the 1-year incidence of nephrolithiasis among human immunodeficiency virus type 1-infected patients treated with indinavir. One hundred three patients (13.6%) developed 326 episodes of nephrolithiasis. Eighty-two patients (79.6%) had more than one episode (range, two to seven episodes). The overall incidence ranged from 0 to 10.2 episodes per 100 patients exposed per month. There was a significant correlation between temperature and the overall incidence of nephrolithiasis and the incidence of recurrences but not with the incidence of first episodes. Nephrolithiasis was not related to humidity or atmospheric pressure. Our data support the standard recommendation of drinking at least 1.5 L of water daily to prevent nephrolithiasis in most patients treated with indinavir irrespective of meteorologic factors. However, the risk of nephrolithiasis is higher for a certain subgroup of patients when the environment is hot irrespective of adequate water intake.  (+info)

Effect of increased pressure on tracheal ciliary beat frequency. (7/437)

Effects of increased ambient pressure on mucociliary clearance have been poorly investigated. The effects of increasing pressures on ciliary beat frequency (CBF) of guinea-pig tracheal rings were studied in vitro. Increased pressures of 25 and 100 kPa induced a significant and equivalent enhancement of CBF from 30 min after the pressure increase. The increase in CBF observed after a pressure increase of 50 kPa (inspiratory oxygen fraction = 21%), was significantly greater than that observed with an equivalent oxygen tension at atmospheric pressure, i.e. with a gas mixture containing 30% oxygen. Addition of N(G)-nitro-L-arginine methylester (L-NAME) inhibited the enhancement in CBF observed after the 25 kPa pressure increase. Addition of L-arginine reversed the effect of L-NAME. These results demonstrate that a pressure increase applied to tracheal rings, in vitro, induces an enhancement of ciliary beat frequency and that generation of nitric oxide may be involved in this ciliary stimulation.  (+info)

Intrapulmonary gas mixing and the sloping alveolar plateau in COPD patients with macroscopic emphysema. (8/437)

Chronic obstructive pulmonary disease patients, especially those with emphysema, show steep slopes of the alveolar plateau (S). This study tested the hypothesis that continued gas exchange between poorly and well-ventilated lung units by means of collateral ventilation would contribute to S in these patients. Nine young volunteers, nine older volunteers and 11 patients with macroscopic emphysema performed wash-out tests with helium (He) and sulphur hexafluoride (SF6). S was determined for breaths 1-5 (range 1), and for breaths between 95% and 98% of complete wash-out (range 2). An unequal ventilation index (UVI) was defined as the ratio between the estimated mean alveolar pressure and the end tidal pressure (PET) of each tracer gas, calculated over range 2. Over the same range, a phase III ratio was calculated by dividing PET by the estimated pressure at Fowler dead space. In all groups of subjects, the S for He and SF6 were greater for range 2 than for range 1 (p< or =0.012). In the emphysema patients, the correlations between S and UVI were 0.72 for He (p=0.012) and 0.81 for SF6 (p=0.002), while the mean phase III ratios were 1.7 for He and 2.4 for SF6, much less than their theoretical maxima. It was concluded that in patients collateral ventilation may account for only a small part of the increase in the alveolar plateau slope between ranges 1 and 2, and that this increase was mainly caused by unequal ventilation in combination with sequential emptying of lung units. The degree of sequential emptying, however, was modest compared with its full potential.  (+info)