正常人心钠素、环磷腺苷、环磷鸟苷、钠和血压、心率昼夜变化的研究

用放射免疫法测定22名(男16,女6)正常人安静卧位时血浆心钠素(ANP)、环磷腺苷(cAMP)、环磷鸟苷(cGMP)在24、8和16时的值,同时测定血清钠(Na)、收缩压(SBP)和心率(HR)值。结果16时值与24时值比较,cAMP(20.1±5.3对14.3±6.9nmol/L,P<0.05),cGMP(6.2±2.4对4.8±1.6nmol/L,P<0.05),ANP(203.4±127.5对64.4±46.0ng/L,P<0.01),Na (14.3±19.3对123,6±26.8nmol/L,P<0.05),SBP(15.7±2.9对14.1±1.9kPa,P<0.05)和HR(80.2±12.4对72.6±10.2次/min,P<0.05)明显升高,而8时与24时比较仅ANP(196.3±140.6ng/L)显著升高(P<0.01),其他各值无明显变化(P>0.05);男女之间各值无差异(P>0.05)。ANP与cAMP、cGMP、Na、SBP和HR无相关(P>0.05)。提示正常人在安静卧位状态下,为维持机体正常代谢,ANP、cAMP、cGMP、Na、SBP和HR呈现的昼夜变化,其值以午夜24时最低,这一变化可能由于伴随心房轻度扩张后,通过神经体液调节从而使上述各值在午夜的分泌抑制出现最低值。     

布洛芬对大鼠体温降低作用的昼夜节律研究

目的:研究布洛芬不同时辰给药对大鼠体温降低作用及血药浓度的昼夜节律变化规律。方法:采用随机区组实验设计,60只大鼠分别在不同时间(2:00、6:00、10:00、14:00、18:00、22:00)单次灌胃给予布洛芬颗粒50mg.kg-1,另取10只为空白对照,观察大鼠体温和血药浓度的昼夜节律变化规律,以时间图和余弦法进行分析。结果:大鼠正常体温及用药后体温均呈现明显的昼夜节律变化,峰值相位及振幅无显著改变,仅均值下降;最佳拟合曲线分别为Yti=38.7+0.52Cos(15°×ti—86.80°)和Yti=37.8+0.55Cos(15°×ti—117°)。大鼠在不同时辰给药血药浓度亦呈现明显的昼夜节律变化,明期血药浓度高于暗期,最佳拟合曲线Yti=41.95+5.30Cos(15°×ti—272.83°)。结论:大鼠在不同时辰给予布洛芬,体温和血药浓度均存在昼夜节律的差异。     

硝苯地平贴片对自发性高血压大鼠血压的作用

以硝苯地平片为对照,研究了硝苯地平贴片对片发性高血压大鼠的降压作用结果表明：Ⅰ能显著降低ＳＨＲ的收缩压,舒张压和平均动脉压,作用强度与剂量呈正相关。高剂量皮肤给药６０ｍｉｎ后,ＳＢＰ,ＤＢＰ,ＭＡＰ分别降低１４．８０％,１６．６４５和１５．９９％,至２４０ｍｉｎ时,ＳＢＰ,ＤＢＰ,ＭＡＰ分别降低一３２．４７％,４１．２９％和３５．０２％。     

Effects of Concentrated Ambient Particles on Heart Rate,Blood Pressure,and Cardiac Contractility in Spontaneously Hypertensive Rats

Epidemiological studies have shown that particulate matter (PM) air pollution is associated with cardiovascular mortality and morbidity, especially for particles with aerodynamic diameters under 2.5 μm (PM_2.5). Recent studies have revealed an association between PM pollution and autonomic functions including heart rate (HR), blood pressure (BP), and heart-rate variability. However, the association and linking mechanisms have not been clearly demonstrated in animal studies. Utilizing a novel approach that employs a mixed-effects model to overcome the problems of variations in diseased animals and circadian cycles, we have previously demonstrated an association between concentrated PM_2.5 and changes of HR and BP in pulmonary hypertensive rats. The objective of this study is to test the plausibility of this methodology and to demonstrate the particle effects under different pathophysiology. The feasibility of cardiac contractility (measured as QA interval, QAI) as an indicator for PM toxicology was also explored. Four spontaneously hypertensive (SH) rats were repeatedly exposed to concentrated PM_2.5 during spring and summer. The mass concentration of particles during the 5 h of exposure was 202.0 ± 68.8 (mean ± SE) and 141.0 ± 54.9 μg/m³ for spring and summer experiments, respectively. During spring exposures, the maximum increase of HR and mean BP noted at the end of exposure were 51.6 bpm (p < .001) and 8.7 mm Hg (p = .002), respectively. The maximum decrease of QAI noted at the same time was 1.6 ms (p = .001). Though a similar pattern was demonstrated during summer exposures, the responses were less prominent. We conclude that concentrated PM_2.5 may increase HR and mean BP and decrease QAI in SH rats. Our results also show that QAI may be used as an indicator in PM toxicology.     

Effects of Nitro-L-Arginine on Blood Pressure and Cardiac Index in Anesthetized Rats: A Pharmacokinetic-Pharmacodynamic Analysis

Purpose. Nitric oxide synthase (NOS) inhibitors such as Nitro-L-arginine (L-NA) are being considered for the management of hypotension observed in septic shock. However, little information is available regarding the pharmacokinetic and pharmacodynamic properties of these agents. Our objective was to examine the relationships between L-NA plasma concentration and various hemodynamic effects such as cardiac index (CI), mean arterial pressure (MAP), and heart rate (HR) elicited by L-NA administration in rats. Methods. L-NA was infused at doses between 2.5 – 20 mg/kg/hr in anesthetized rats over one hour. Hemodynamic effects and plasma L-NA levels were determined. Results. Infusion of L-NA resulted in dose-dependent increases in MAP and systemic vascular resistance (SVR), decreases in CI, and minimal change in HR. The relationships between the hemodynamic effects and plasma L-NA levels were not monotonic, and hysteresis was observed. Using nonparametric analysis, the equilibration half-time (t_1/2,keo) between plasma L-NA and the hypothetical effect site was determined to be 51.5 ± 6.6 min, 42.4 ± 10.1 min, 43.4 ± 9.0 min for MAP, CI, and SVR, respectively (n = 14). The E_max and EC₅₀ values obtained were + 32.5 ± 8.4 and 2.6 ± 1.3 g/ml for MAP and –52.9 ± 15.6 and 3.7 ± 1.8 g/ml for CI, respectively. Conclusions. Although L-NA can bring about beneficial elevation of MAP, such effect is always accompanied by a stronger effect on CI depression. Dose escalation of L-NA may bring about detrimental negative inotropic effect and loss of therapeutic efficacy.     

Effects of Concentrated Ambient Particles on Heart Rate,Blood Pressure,and Cardiac Contractility in Spontaneously Hypertensive Rats During a Dust Storm Event

Epidemiological studies have suggested that cardiovascular mortality and morbidity increased during Asian dust events. The findings were still inconclusive though. We have shown an increased pulmonary toxicity in diseased animals during a dust storm event. However, the toxicity nature of dust storm particles remains unclear. It is our objective in this study to further investigate the cardiovascular effects of concentrated PM_2.5 on spontaneously hypertensive rats during the same dust storm event. Four spontaneously hypertensive rats were implanted with radiotelemetry transmitters at the age of 10 wk. Baseline heart rate, mean blood pressure, and cardiac contractility (measured as QA interval, QAI) data were collected 4 wk before. Exposure group received concentrated ambient particles inhalation for 6 h during a dust storm event, while the control group received room air inhalation at the same time. Self-control data were collected 4 wk after the event during the same clock hours while there was no dust storm. Gravimetric analysis showed a particle mass concentration of 315.55 μg/m³ during the 6 h of exposure. A linear mixed-effects model revealed sigmoid increases in heart rate (to a maximum of 93.8 ± 18.8 bpm) and mean blood pressure (to a maximum of 14.8 ± 5.4 mm Hg), and a sigmoid decrease of QAI (to a maximum of ? 3.5 ± 1.5 ms) during the exposure after an initial incubation period. We conclude that concentrated dust storm particles, which are different from products of automobile combustion process, may cause adverse cardiovascular effects on diseased animals.