The relationship between long bone growth rate and duodenal calcium transport in female rats.

Studies were carried out to determine the relationship between long bone growth and duodenal calcium (Ca) transport in female rats and the regulation of these two parameters by ovarian hormones. Female rats were ovariectomized (ovx) at 6 weeks of age. Some animals were implanted with silastic implants containing either estradiol or progesterone at the time of ovx. Studies were carried out 3 weeks later when the rats were 9 weeks old. Ovx resulted in an increase in long bone growth rate and duodenal Ca transport without any alteration in circulating levels of parathyroid hormone or 1,25-dihydroxyvitamin D [1,25-(OH)2D]. Animals receiving estradiol exhibited decreased long bone growth rate and duodenal Ca transport relative to ovx animals. These animals were mildly hypercalcemic and had lower levels of 1,25-(OH)2D than ovx or intact animals. The results of these studies suggest that the effects of ovarian hormone status on duodenal Ca transport are more closely related to long bone growth rate than to circulating levels of 1,25-(OH)2D. Further studies are required to determine whether the two parameters are coregulated by some as-yet-unidentified factor or whether bone growth is able to emit some signal, directly or indirectly, to increase duodenal Ca transport.

Dopaminergic agonists increase [3H]estradiol binding in hypothalamus of female rats, but not of males.

Specific nuclear binding of [3H]estradiol in the hypothalamus was increased by acute dopaminergic treatment in female, but not in male, gonadectomized-adrenalectomized rats. In the female this increase could be blocked by the dopaminergic receptor blocker perphenazine and was noted from 1 to 3 hours after injection of [3H]estradiol. Binding was not different in male and female rats in the absence of dopaminergic treatment. These results suggest that acute dopaminergic stimulation may modulate estradiol binding in neural areas known to be important in endocrine function.

Regulation of duodenal insulin-like growth factor I and active calcium transport by ovariectomy in female rats.

There is a significant body of data that supports the concept that reproductive hormones in females have effects on duodenal calcium transport that are not mediated via altered circulating concentrations of 1,25-dihydroxyvitamin D (1,25(OH)2D). Previously, we have shown parallel alterations in duodenal Ca transport and longitudinal bone growth rate in sexually maturing female rats in response to ovariectomy and estradiol (E) treatment of ovariectomized (OVX) rats (OVX+E) without any change in circulating levels of 1,25(OH)2D or parathyroid hormone. Results are presented here from experiments designed to: (i) further explore the relationship between 1,25(OH)2D and ovarian status in the regulation of duodenal calcium transport, and (ii) determine whether OVX and E replacement alter circulating and duodenal levels of insulin-like growth factor I (IGF-I) that might be related to effects on Ca transport. Growth hormone, which has been shown to affect intestinal Ca absorption and vitamin D metabolism, is thought to act indirectly by stimulating IGF-I. Six-week-old female rats were OVX, given estradiol implants (OVX+E), and fed a diet containing either 0.5% or 0.1% Ca for 3 weeks. In both diet groups, the OVX animals exhibited a higher level of Ca transport, as measured by the everted gut sac method, than either the intact controls or the OVX+E group; there was no difference in calcium transport between the different diet groups. Although there was no difference in circulating levels of 1,25(OH)2D among the intact, OVX, and OVX+E groups fed either diet, animals fed the 0.1% Ca diet had higher circulating levels of 1,25(OH)2D than those fed the 0.5% Ca diet. There was no difference in duodenal levels of calbindin9K among intact, OVX, and OVX+E animals in either diet group, although the animals fed the 0.1% Ca diet had higher levels of calbindin9K than the animals fed the 0.5% Ca diet. In animals fed the 0.5% Ca diet, OVX resulted in elevated serum and duodenal levels of IGF-1, as compared with intact and OVX+E animals on the same diet. In animals fed the 0.1% Ca diet, there was no elevation of IGF-I in the OVX group relative to intact and OVX+E animals. These results lend additional support to the concept that alterations in duodenal active calcium transport that occur with alterations in ovarian hormones are not mediated by changes in serum levels of 1,25(OH)2D, but may be related to some factor related to growth, possibly IGF-I.

Testosterone alters duodenal calcium transport and longitudinal bone growth rate in parallel in the male rat.

Duodenal active calcium transport and longitudinal bone growth rate have been shown previously to be regulated in parallel by alteration of gonadal hormone status in sexually maturing female rats. The present study was designed to extend these observations to the sexually maturing male rat. Male rats were orchidectomized (ORX) and given Silastic implants containing either testosterone or estradiol at 6 weeks of age. At 9 weeks of age, duodenal active calcium transport was measured by the everted gut sac method and longitudinal bone growth rate was determined by tetracycline labeling. Decreases in body weight, longitudinal bone growth rate, duodenal calcium transport, and serum Ca and P were exhibited by ORX animals as compared with age-matched control animals. Testosterone administration to ORX animals resulted in an increase in body weight, longitudinal bone growth rate, duodenal calcium transport, and serum Ca and P as compared with ORX animals to a level not significantly different from that of age-matched control animals. Estradiol administration to ORX animals resulted in an additional decrease in body weight, although no significant effect on duodenal calcium transport, serum Ca, or P was noted as compared with ORX animals. There were no statistically significant alterations in the circulating levels of 1,25-dihydroxyvitamin D, parathyroid hormone, or osteocalcin in response to any of the experimental manipulations of gonadal status. These results indicate that, as in the female, gonadal hormone status affects intestinal calcium transport in sexually maturing male rats in parallel with changes in bone growth rate by mechanisms that are independent of circulating levels of 1,25-dihydroxyvitamin D.

Site(s) mediating sympathetic activation with desflurane.

BACKGROUND: Three strategies were employed to better define the afferent site(s) at which desflurane initiates its neurocirculatory activation. METHODS: Young (aged 19-28 yr) healthy volunteers were employed in three separate studies. Monitoring included electrocardiography, radial artery blood pressure, and direct recordings of sympathetic outflow to skeletal muscle blood vessels by microneurography. In each study, anesthesia was established with 2.5 mg/kg propofol, and in studies 1 and 2 was maintained with 5.4% desflurane via a double-lumen tube. In study 1 (n = 7) a double-lumen tube was placed with the bronchial cuff just below the vocal cords to selectively give 14.5% desflurane or 2.4% isoflurane to the upper airway (via the tracheal lumen) or lower airway (via the bronchial lumen). Study 2 (n = 14) consisted of standard placement of a left side double-lumen tube to selectively increase the inspired desflurane concentration of either right or left lung to 11% while decreasing the inspired concentration in the opposite lung to 0%, thereby maintaining constant systemic concentrations of desflurane (gas chromatography). Study 3 consisted of lidocaine or placebo airway treatment before anesthetic induction and administration of 11% inspired desflurane by mask: group A-n = 9, topical and nebulized lidocaine, glossopharyngeal and superior laryngeal nerve blocks, and transtracheal administration of lidocaine; group B-n = 7, similar treatment as group A with placebo (saline); and group C-n = 8, systemic infusions of 2% lidocaine to match plasma concentrations of lidocaine in group A. RESULTS: In study 1, significant increases in heart rate, mean arterial pressure, and sympathetic neural activity (26%, 23%, and 62%, respectively) occurred when desflurane was directed to the upper airway. These responses were approximately twofold to sixfold larger when desflurane was given to the lower airway (lungs). There were no significant increases in these variables when isoflurane was administered to the upper airways, and a significant increase in heart rate occurred only when isoflurane was delivered to the lower airways. In study 2, separate right or left lung increases in desflurane did not change the blood concentration of desflurane or sympathetic neural activity but led to significant increases in heart rate (44%) and mean arterial pressure (32%). The simultaneous administration of desflurane to both lungs increased the millimolar (mM) concentration of desflurane in the blood from 1.17 to 2.39 mM and led to increases in sympathetic neural activity (750%), heart rate (90%), and mean arterial pressure (63%). In study 3, neither regional nor systemic administration of lidocaine reduced the significant neurocirculatory activation caused by the rapid increase in the inspired concentration of desflurane by mask. CONCLUSIONS: There are sites in the upper airway (larynx and above) that respond with sympathetic activation during rapid increases in desflurane concentration independent of systemic anesthetic changes. These responses, while lesser than those seen with rapid increases to the lung, may represent direct irritation of airway mucosa. Heart rate and mean arterial pressure responses to desflurane can be initiated by selectively increasing concentrations to either right or left lung without altering systemic levels of desflurane. From this it is inferred that there are sites within the lungs, separate from systemic sites, that mediate this response. Neither systemic lidocaine nor attempted blockade of upper airway sites with cranial nerve blocks combined with topical lidocaine was effective in attenuating the neurocirculatory activation associated with desflurane.

Alfentanil modifies the neurocirculatory responses to desflurane.

Activation of the sympathetic nervous system occurs in response to desflurane, causing tachycardia and hypertension. Fentanyl partially blunts the hemodynamic effects of desflurane but fails to attenuate the sympathetic response. This study determined the clinical effectiveness and dose response of alfentanil on the neurocirculatory responses to desflurane. Twenty-five healthy, male volunteers were randomized into one of three groups to receive either placebo (n = 9), 10 micrograms/kg intravenous (IV) bolus alfentanil (n = 9), or 20 micrograms/kg IV bolus alfentanil (n = 7) in conjunction with anesthetic induction by propofol, 2.5 mg/kg. Mean arterial pressure (MAP, radial artery), heart rate (HR), and efferent muscle sympathetic nerve activity (SNA, peroneal nerve) were recorded. After conscious baseline measurements, anesthesia was induced by propofol and alfentanil/placebo. One minute later, the desflurane vaporizer was activated at 11%. Neurocirculatory measurements were recorded for 11 min. There were no differences between the groups at conscious baseline. Induction of anesthesia was associated with significantly decreased MAP in the placebo and the 10 micrograms/kg alfentanil groups and increased HR in all groups with little change in SNA. In placebo subjects, desflurane administration increased HR and MAP above baseline. In both alfentanil groups, during desflurane administration HR and MAP never increased significantly above baseline. However, SNA was significantly increased in both groups. Alfentanil effectively blunts the hemodynamic changes but not the sympathetic responses associated with rapid increases in the inspired concentration of desflurane.