Bell-shaped relationship between central blood volume and spontaneous baroreflex function.

Spontaneous baroreflex function can be altered by acute changes in central blood volume. Both a reduction in spontaneous baroreflex function at central hypovolemia and augmentation at hypervolemia suggest a dose-effect relationship between central blood volume and spontaneous baroreflex function. However, this relationship has not been quantified over stepwise widespread changes in central blood volume. Twelve individuals underwent central hypovolemia at two levels of lower body negative pressure (LBNP) (-15 mm Hg, LBNP15; -30 mm Hg, LBNP30) and hypervolemia with two discrete infusions of normal saline (NS) (15 ml kg(-1), NS15; total 30 ml kg(-1), NS30). Spontaneous baroreflex function was assessed using transfer function analysis and the sequence method between blood pressure and R-R interval. Both central venous pressure (-0.6-7.9 mm Hg) and left ventricular end-diastolic volume (72.4-133.1 ml) decreased during LBNP and increased after saline infusion. Both spontaneous baroreflex indices of high-frequency transfer function gain (LBNP30, 17.4+/-3.2; LBNP15, 22.3+/-3.8; baseline, 25.6+/-4.1; NS15, 28.5+/-4.2 ms mm Hg(-1), ANOVA P=0.001) and of the sequence slope (LBNP30, 14.4+/-2.2; LBNP15, 17.2+/-2.5; baseline, 20.5+/-2.8; NS15, 24.5+/-3.1 ms mm Hg(-1), ANOVA P=0.001) increased stepwise from hypovolemia of LBNP30 to hypervolemia of NS15. However, these indices were lower at NS30 (high-frequency transfer function gain, 22.0+/-2.2 ms mm Hg(-1), post-hoc P=0.071; sequence slope, 17.7+/-1.7 ms mm Hg(-1), post-hoc P<0.05) than NS15 during hypervolemia. These results indicated that the relationship between central blood volume and spontaneous baroreflex function is apparently bell-shaped, with maximal augmentation at moderate hypervolemia.

UCN-01 (7-hydroxystaurosporine) induces apoptosis and G1 arrest of both primary and metastatic oral cancer cell lines in vitro.

OBJECTIVE: Our aim was to clarify the in vitro antiproliferative effects of UCN-01 on human oral squamous cell carcinoma (OSCC) cell lines. STUDY DESIGN: Cell growth was measured by MTT assay, and cell cycling was assessed by flow cytometry. Changes in the levels of protein and protein phosphorylation were analyzed by Western blotting. In addition, tumor cell apoptosis was assessed by propidium iodide (PI) and annexin double-staining. RESULTS: UCN-01 significantly inhibited the proliferation of all the OSCC cell lines, with a 50% inhibition concentration of about 300 nmol/L, and induced G1 arrest in these cell lines in a dose-dependent manner. Primary and metastatic oral cancer cell lines had different sensitivities to UCN-01. Our results showed that HSC-3 cells (primary-type OSCC) are less sensitive than LMF4 cells (metastatic-type OSCC) to UCN-01. In addition, the induction of p21 in OSCCs was found to be important for the suppression of tumor growth. CONCLUSION: The results of this study suggest that UCN-01 induces apoptosis and G1 arrest in OSCCs, albeit with different sensitivity of the primary and metastatic cell lines to UCN-01.

Cardiovascular regulation response to hypoxia during stepwise decreases from 21% to 15% inhaled oxygen.

INTRODUCTION: The classical view states that hypoxia beyond an oxygen concentration of about 17% induces tachycardia. However, few studies have investigated the dose-dependent effects of acute normobaric hypoxia on autonomic nervous regulation of the cardiovascular system. Therefore, we evaluated the effects of stepwise hypoxia on cardiovascular neural regulation and postulated that acute normobaric hypoxia causes vagal withdrawal and sympathetic activation from 17% 02. METHODS: There were 18 healthy men who were exposed to acute stepwise normobaric hypoxia (21%, 19%, 17%, 15% 02). Spectral analysis of the RR interval and BP variability were used. RESULTS: BP was not altered. Heart rate significantly increased at 15% (21%, 59 +/- 2; 15%, 62 +/- 2 bpm). The low-frequency power of systolic BP variability (an index of vasomotor sympathetic nerve activity) significantly increased at 15% (21%, 6.1 +/- 1.3; 15%, 9.9 +/- 1.3 mmHg2). The low-frequency power of the RR interval variability significantly increased from 17% (21%, 1036 +/- 233; 17%, 1892 +/- 409; 15%, 1966 +/- 362 ms2), However, the high-frequency power of RR interval variability (an index of cardiac parasympathetic nerve activity) did not change. Associated with these changes, the ratio of low- to high-frequency power of RR interval variability as an index of relative cardiac autonomic balance significantly shifted toward sympathetic dominance (21%, 1.5 +/- 0.3; 15%, 2.2 +/- 0.3). All indices of cardiac baroreflex function (transfer function and sequence gains) were unchanged. DISCUSSION: These results suggest that acute exposure to normobaric mild hypoxia (O2 > or = 15%) induces increases in sympathetic vasomotor activity and cardiac sympathetic dominance resulting in an increased heart rate. However, 15% O2 hypoxia might not induce changes in static BP, vagal activity, or spontaneous arterial-cardiac baroreflex function.

Dose-dependent effects of hypergravity on body mass in mature rats.

INTRODUCTION: Previous reports have shown that exposure to hypergravity decreases rat body mass during the initial phase, with this decrease and level of gravity showing a dose-response relationship. The present study examined whether rate of body mass gain after the initial phase of exposure is attenuated by hypergravity in a dose-dependent manner and sought to identify any threshold. METHODS: Male 10-wk-old rats (n = 64) were used, with 16 rats serving as 1.0-G controls, and 48 rats exposed to hypergravity for 14 d in 4 groups (1.5, 2.0, 2.5, and 3.5 G; n = 12 each). Body mass gain was evaluated according to slope of change in body mass from day 7 of exposure to hypergravity, as both absolute and relative values. RESULTS: Slopes of body mass gain did not differ between the 1.0- and 1.5-G groups (6.09 and 5.75 g x d(-1), respectively), but were significantly less for the 2.0-, 2.5-, and 3.5-G groups (4.91, 3.03 and 1.99 g x d(-1), respectively) than for the 1.0- and 1.5-G groups. Body mass gain as a relative value did not differ between the 1.0-, 1.5-, and 2.0-G groups (1.5 +/- 0.2, 1.6 +/- 0.6 and 1.4 +/- 0.3 g x d(-1) x 100 g(-1) body mass, respectively), but was significantly less for the 2.5- and 3.5-G groups (1.1 +/- 0.6 and 0.8 +/- 0.3 g x d(-1) x 100 g(-1) body mass, respectively) than for the 1.0-, 1.5-, and 2.0-G groups. Absolute values and rate of body mass gain were reduced with increases in gravity. CONCLUSION: Exposure to hypergravity attenuates body mass gain in a dose-dependent manner, with a threshold possibly existing between 1.5- and 2.5-G for 10-wk-old male rats.