Mechanisms of vasodilation to PTH 1-84, PTH 1-34, and PTHrP 1-34 in rat bone resistance arteries.

UNLABELLED: Parathyroid hormone (PTH) augments bone metabolism and bone mass when given intermittently. Enhanced blood flow is requisite to support high tissue metabolism. The bone arteries are responsive to all three PTH analogs, which may serve to augment skeletal blood flow during intermittent PTH administration. INTRODUCTION: PTH augments bone metabolism. Yet, mechanisms by which PTH regulates bone blood vessels are unknown. We deciphered (1) endothelium-dependent and endothelium-independent vasodilation to PTH 1-84, PTH 1-34, and PTHrP 1-34, (2) the signaling pathways (i.e., endothelial nitric oxide synthase [eNOS], cyclooxygenase [COX], protein kinase C [PKC], and protein kinase A [PKA]), and (3) receptor activation. METHODS: Femoral principal nutrient arteries (PNAs) were given cumulative doses (10(-13)-10(-8) M) of PTH 1-84, PTH 1-34, and PTHrP 1-34 with and without signaling pathway blockade. Vasodilation was also determined following endothelial cell removal (i.e., denudation), PTH 1 receptor (PTH1R) inhibition and to sodium nitroprusside (SNP; a nitric oxide [NO] donor). RESULTS: Vasodilation was lowest to PTH 1-34, and maximal dilation was highest to PTHrP 1-34. Inhibition of eNOS reduced vasodilation to PTH 1-84 (-80 %), PTH 1-34 (-66 %), and PTHrP 1-34 (-48 %), evidencing the contribution of NO. Vasodilation following denudation was eliminated (PTH 1-84 and PTHrP 1-34) and impaired (PTH 1-34, 17 % of maximum), highlighting the importance of endothelial cells for PTH signaling. Denuded and intact PNAs responded similarly to SNP. Both PKA and PKC inhibition diminished vasodilation in all three analogs to varying degrees. PTH1R blockade reduced vasodilation to 1, 12, and 12 % to PTH 1-84, PTH 1-34, and PTHrP 1-34, respectively. CONCLUSIONS: Vasodilation of femoral PNAs to the PTH analogs occurred via activation of the endothelial cell PTH1R for NO-mediated events. PTH 1-84 and PTHrP 1-34 primarily stimulated PKA signaling, and PTH 1-34 equally stimulated PKA and PKC signaling.

Kinetic examination of femoral bone modeling in broilers.

Lameness in broilers can be associated with progressive degeneration of the femoral head leading to femoral head necrosis and osteomyelitis. Femora from clinically healthy broilers were dissected at 7 (n = 35, 2), 14 (n = 32), 21 (n = 33), 28 (n = 34), and 42 (n = 28) d of age, and were processed for bone histomorphometry to examine bone microarchitecture and bone static and dynamic properties in the secondary spongiosa (IISP) of the proximal femoral metaphysis. Body mass increased rapidly with age, whereas the bone volume to tissue volume ratio remained relatively consistent. The bone volume to tissue volume ratio values generally reflected corresponding values for both mean trabecular thickness and mean trabecular number. Bone metabolism was highest on d 7 when significant osteoblast activity was reflected by increased osteoid surface to bone surface and mineralizing surface per bone surface ratios. However, significant declines in osteoblast activity and bone formative processes occurred during the second week of development, such that newly formed but unmineralized bone tissue (osteoid) and the percentages of mineralizing surfaces both were diminished. Osteoclast activity was elevated to the extent that measurement was impossible. Intense osteoclast activity presumably reflects marked bone resorption throughout the experiment. The overall mature trabecular bone volume remained relatively low, which may arise from extensive persistence of chondrocyte columns in the metaphysis, large areas in the metaphysis composed of immature bone, destruction of bone tissue in the primary spongiosa, and potentially reduced bone blood vessel penetration that normally would be necessary for robust development. Delayed bone development in the IISP was attributable to an uncoupling of osteoblast and osteoclast activity, whereby bone resorption (osteoclast activity) outpaced bone formation (osteoblast activity). Insufficient maturation and mineralization of the IISP may contribute to subsequent pathology of the femoral head in fast-growing broilers.

L-carnitine supplementation does not promote weight loss in ovariectomized rats despite endurance exercise.

In this five-week study, we tested the hypotheses that free access to a maintenance diet supplemented with L-carnitine (L-C) would reduce body fat in adult, sedentary, ovariectomized (OVX) rats, and that there would be an additive effect of L-C on weight reduction in swim-trained animals. As expected, serum carnitine was higher in rats fed the L-C diet, and the OVX-induced weight gain and abdominal fat were counteracted by swimming. L-C supplementation did not reduce the weight gain or abdominal fat in these adult female rats, Moreover, though not reaching statistical significance, rats that were fed L-C demonstrated a tendency for greater weight gain than their basal-fed counterparts despite no difference in energy intake. If the results of this study on ovariectomized rats can be translated to postmenopausal women, moderate intensity exercise may be recommended, but L-C supplementation, with no energy restriction, may be contraindicated as a weight loss method in this cohort.

Modification of forearm vascular function following short-term handgrip exercise training.

This study examined the effect of low (25% of maximum voluntary contraction) and high (75% of maximum voluntary contraction) intensity short-term handgrip exercise training on localized vascular function. Forearm blood flow was evaluated in twenty-eight healthy men (age: 23 +/- 4.3) pre- and post-training in both forearms at rest, following forearm occlusion and following forearm occlusion combined with handgrip exercise using strain gauge plethysmography. The 4-week program consisted of non-dominant handgrip exercise performed 5 d/wk for 20 min at either low or high intensity. Following training a significant increase in forearm blood flow was noted for the nondominant arm in both groups after forearm occlusion (low intensity group: 16.51%; high intensity group: 20.72%; p = 0.001) and forearm occlusion combined with handgrip exercise (low intensity group: 17.71%; high intensity group: 29.27%; p = 0.001). No significant group by test interaction (p = 0.632) was found. These data show improved unilateral vasodilatory responsiveness after short-term handgrip training. In addition, the degree of change is most notable following the greatest vasodilatory stimulus. Lastly, a lack of group by treatment interaction suggests the change may be independent of training stimulus.

Thermal sensation and substrate utilization differs among low- and high-fat women exposed to 17 degrees C water.

OBJECTIVE: Thermal sensation and the physiological responses of women (follicular phase) exposed to 17 degrees C immersion for 120 minutes were investigated. METHODS: The subjects were divided into 2 groups by percent body fat (low fat [LF] = 21% +/- 2% [mean +/- SD] vs high fat [HF] = 30% +/- 3%). A 2-way analysis of variance was used to determine differences between the groups in metabolism, metabolism derived from carbohydrate, metabolism derived from fat, blood glucose, rectal temperature, skin temperature, and thermal sensation. RESULTS: As anticipated, pooled metabolism increased across the 120-minute immersion. Metabolism derived from carbohydrate was significantly higher in the LF than in the HF group and increased across time. Blood glucose decreased significantly across time, yet there was no group difference, suggesting that the LF group may have utilized a greater proportion of intramuscular glycogen. The HF group demonstrated a higher rectal temperature compared to their LF counterparts. Overall, rectal temperature demonstrated a group x time interaction as immersion continued. However, rectal temperature for all subjects remained above 35 degrees C. Surprisingly, the HF group perceived significantly greater thermal discomfort than did their LF counterparts. CONCLUSIONS: Since intramuscular glycogen utilization is associated with shivering thermogenesis, the suspected greater utilization of this fuel by the LF group may have contributed to less thermal discomfort than in the HF group. However, since glycogen utilization was not directly measured, this speculation cannot be validated. It is also possible that the modified thermal sensation scale we used may not be an adequate marker of thermal discomfort in females with a high percentage of body fat (28% to 35%) exposed to cold water immersion.

Thermal and metabolic responses of high and low fat women to cold water immersion.

BACKGROUND: At rest during cold exposure, the amount of body fat plays an important role in the maintenance of core temperature. High fat (HF) individuals would therefore have an advantage as compared with their low fat (LF) counterparts. Since females usually have a higher amount of body fat than males they are expected to maintain core temperature at a lower energy cost. METHODS: The purpose of the present investigation was to dichotomize female subjects by percent fat (LF = 20.5 +/- 2%, n = 6 vs. HF = 30 +/- 3%, n = 6) to elucidate the thermal and metabolic responses during acute exposure to 17 degrees C water for 120 min. The following variables were measured: rectal temperature (Tre; degrees C), mean skin temperature (Tsk; degrees C), oxygen consumption (VO2; ml x kg(-1) x min(-1)), and tissue insulation (I; degrees C x m2 x W(-1)). The experiment-wise error rate was set a priori at p = 0.05. RESULTS: Unexpectedly, only one of the variables demonstrated a main effect for fat (p < 0.05). Tre demonstrated a significant (p < 0.05) group by time interaction. However, Tsk and I demonstrated a main effect for time (p < 0.05). While VO2 demonstrated an increase across time, these changes were non-significant (p > 0.05). It appears that the HF group demonstrated a similar thermal (I and Tsk) and metabolic (VO2) response as compared with the LF counterparts. However, the LF groups maintained a lower Tre as compared with the HF subjects. Perhaps leaner subjects or colder water temperatures would elucidate the value of body fat in females, and demonstrate a differential response with respect to females varying in percent body fat.

Thermal and metabolic responses of women with high fat versus low fat body composition during exposure to 5 and 27 degrees C for 120 min.

BACKGROUND: Men with high fat body composition maintain higher core temperatures, and lower aerobic metabolic rates than their low fat counterparts thus, verifying the insulatory benefit of body fat. Females, on average have more body fat and less muscle mass than males, and may maintain rectal temperature (Tre) at a lower energy cost. METHODS: The present investigation dichotomized female subjects by percent fat (low fat; n = 3, LF = 19.2+/-3% vs. high fat; n = 4 HF: 29.9+/-3%) to elucidate the thermal and metabolic responses during acute exposure to 5 and 27 degrees C air for 120 min. An ANOVA was used to examine the following: Tre (degrees C), mean skin temperature (Tsk; degrees C), oxygen consumption (VO2; ml x kg(-1) x min(-1)) and tissue insulation (I; degrees C x m2 x W(-1)). For Tre, a significant fat x time interaction (p < 0.05) was demonstrated at both 5 and 27 degrees C, whereby Tre tended to be lower in the LF group than the HF group. VO2 at 5 degrees C demonstrated a main effect for time only. For I, a main effect for time was noted at 5 degrees C. Also for I, a trend (p = 0.06) toward a main effect of fat during exposure to 5 degrees C was noted while at 27 degrees C a main effect (p < 0.05) was demonstrated. RESULTS: From this data it appears that under these conditions, the HF group demonstrated higher Tre and I values than their LF counterparts that was not accompanied with a differential response with respect to aerobic metabolic rate. Thus, the impact of body composition on energy expenditure to maintain Tre differs between LF and HF males and females.

The perceptual and physiological responses of high and low fat women exposed to 5 degrees C air for 120 minutes.

The present investigation dichotomized female subjects by percentage of fat (low fat [LF] = 19.2+/-3% [n = 4] vs high fat [HF] = 29.9+/-3% [n = 4]) to elucidate the perceptual and physiological responses during acute exposure to 5 degrees C air for 120 min. Correlational analyses were used to assess the relationship between thermal sensection (TS) and differences between LF and HF groups. Significant (p < 0.01) differences existed between the groups for TS when values were pooled over time, where HF had a lower TS (5.9+/-0.6) than LF (7.9+/-0.5). Additionally, a significant (p < 0.01) main effect for time existed, where TS, when pooled over groups T5 (3.8+/-0.7) and T30 (5.4+/-0.9), was less than T60 (7.4+/-0.6), T90 (8.6+/-0.5), and T120 (9.1+/-0.4). No significant fat x time interaction was noted despite apparent perceptual differences between the groups at most of the time points. Further, the relationships between TS and percentage of fat and fat mass were either significant or exhibited strong trends toward significance at time points T5, T30, and T60. When rectal temperature (Tre) was pooled over the four time points, the fat groups differed significantly (p < 0.05); LF (-0.21+/-0.04 degrees C) exhibited a greater ATre than HF (-0.03+/-0.04 degrees C). When Tre was pooled across the fat groups, significant (p < 0.01) differences over time were detected. From these data, it appears that the modified TS scale tested may be a good marker of thermal discomfort in females exposed to the cold because perceptual differences were noted between the groups, accompanied by apparent differences in Tre between the LF and HF groups.