Background-Endothelium-dependent dilatation is mediated by 3 principal vasodilators: nitric oxide (NO), prostacyclin (PGI 2 ), and endothelium-derived hyperpolarizing factor (EDHF). To determine the relative contribution of these factors in endothelium-dependent relaxation, we have generated mice in which the enzymes required for endothelial NO and PGI 2 production, endothelial NO synthase (eNOS) and cyclooxygenase-1 (COX-1), respectively, have been disrupted (eNOS Ϫ/Ϫ and COX-1 Ϫ/Ϫ mice). Methods and Results-In female mice, the absence of eNOS and COX-1 had no effect on mean arterial blood pressure (BP), whereas BP was significantly elevated in eNOS Ϫ/Ϫ /COX-1 Ϫ/Ϫ males compared with wild-type controls. Additionally, endothelium-dependent relaxation remained intact in the resistance vessels of female mice and was associated with vascular smooth muscle hyperpolarization; however, these responses were profoundly suppressed in arteries of male eNOS Ϫ/Ϫ /COX-1 Ϫ/Ϫ animals. Similarly, the endothelium-dependent vasodilator bradykinin produced dose-dependent hypotension in female eNOS Ϫ/Ϫ /COX-1 Ϫ/Ϫ animals in vivo but had no effect on BP in male mice. Conclusions-These studies indicate that EDHF is the predominant endothelium-derived relaxing factor in female mice, whereas NO and PGI 2 are the predominant mediators in male mice. Moreover, the gender-specific prevalence of EDHF appears to underlie the protection of female eNOS

Bone mineral content (BMC), bone mineral density, and metacarpal dimensions were studied in 50 women with Turner's syndrome aged 21-45 years in relation to karyotype, estrogen treatment, physical fitness, and biochemical markers of bone turnover. No differences were found between the 25 women with karyotype 45.X and women with other karyotypes. Forty-six women had received estrogen. Significant partial correlations were found between bone mineral density of the forearm and duration of estrogen treatment and physical fitness. BMC of the lumbar spine corrected for vertebral height (BMC(C)spine) was directly correlated with duration of estrogen treatment and height, marginally correlated with physical fitness, and inversely correlated with age. Outer metacarpal width was positively correlated with duration of estrogen treatment, age at initiation of therapy, and body weight. The diameter of medullary space showed negative correlation with physical fitness and height, and positive correlation with age at initiation of estrogen treatment. Cortical thickness was positively correlated with duration of estrogen treatment, physical fitness, and height. No convincing effects of estrogen could be demonstrated in women below the age of 30. Above the age of 30, all bone mineral measurements were markedly elevated in women treated for longer than the average of this age group. BMC(C)spine was inversely correlated with biochemical markers of bone formation. Our results demonstrate that estrogen treatment and physical fitness are important determinants of bone mineral status in Turner's syndrome and add to the evidence that estrogen treatment increases BMC in Turner's syndrome.

No abstract

Aim:This study aimed to assess intracellular Ca 2+ dynamics in nerve cells and Schwann cells in isolated rat resistance arteries and determine how these dynamics modify noradrenaline release from the nerves and consequent force development. Methods: Ca 2+ in nerves was assessed with confocal imaging, noradrenaline release with amperometry and artery tone with wire myography. Ca 2+ in axons was assessed after loading with Oregon Green 488 BAPTA-1 dextran. In other experiments, arteries were incubated with Calcium Green-1-AM which loads both axons and Schwann cells. Results: Schwann cells but not axons responded with a Ca 2+ increase to ATP.Electrical field stimulation of nerves caused a frequency-dependent increase in varicose [Ca 2+ ] ([Ca 2+ ] v ). ω-conotoxin-GVIA (100 nmol/L) reduced the [Ca 2+ ] v transient to 2 and 16 Hz by 60% and 27%, respectively; in contrast ω-conotoxin GVIA inhibited more than 80% of the noradrenaline release and force development at 2 and 16 Hz. The K V channel blocker, 4-aminopyridine (10 µmol/L), increased [Ca 2+ ] v , noradrenaline release and force development both in the absence and presence of ωconotoxin-GVIA. Yohimbine (1 µmol/L) increased both [Ca 2+ ] v and noradrenaline release but reduced force development. Acetylcholine (10 µmol/L) caused atropinesensitive inhibition of [Ca 2+ ] v , noradrenaline release and force. In the presence of ω-conotoxin-GVIA, acetylcholine caused a further inhibition of all parameters. Conclusion: Modification of [Ca 2+ ] in arterial sympathetic axons and Schwann cells was assessed separately. K V 3.1 channels may be important regulators of [Ca 2+ ] v , noradrenaline release and force development. Presynaptic adrenoceptor and muscarinic receptor activation modify transmitter release through modification of [Ca 2+ ] v . K E Y W O R D S amperometry, confocal imaging, neurotransmission, prejunctional modulation, small arteries, sympathetic 2 of 11 | HANSEN Et Al.