Hyperparathyroidism and abnormal calcitriol metabolism in the spontaneously hypertensive rat.

Merke, J.; Lucas, P. A.; Szabó, András; Cournot-Witmer, Giulia; Mall, Gerhard; Bouillon, Roger; Drüeke, Tilman B.; Mann, Johannes F.E.; Ritz, Eberhard

doi:10.1161/01.hyp.13.3.233

Cited by 40 publications

(14 citation statements)

References 40 publications

(25 reference statements)

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“…Parathyroid function has been shown to be necessary for the development of hypertension in hypertensive rats 12 -14 and parathyroid glands from hypertensive rats demonstrate hypertrophy, 20 yet Pang et al 21 were unable to detect elevations of any serum PTH fragments in spontaneously hypertensive rats during the development of hypertension. PTH has been shown to increase calcium entry into cardiac cells and osteoblastlike cells,…”

Section: Discussionmentioning

confidence: 99%

Parathyroid hormone, platelet calcium, and blood pressure in normotensive subjects.

Brickman¹,

Nyby²,

Hungen³

et al. 1991

Hypertension

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Relations between platelet cytosolic calcium, parathyroid hormone, and blood pressure were investigated in 91 normotensive subjects: 47 men and 44 women ranging in age from 24 to 70 years. The men had higher mean arterial blood pressure, serum creatinine, and body mass index than the women. Serum total calcium, plasma ionized calcium, and parathyroid hormone (measured as both intact hormone and mid-molecule fragment) were not different between men and women; however, serum phosphate was higher in women than in men. Basal platelet cytosolic calcium was higher in men than in women (113.7±1.9 versus 105.9±1.7, respectively; p<0.0l), but there was no difference in the peak platelet cytosolic calcium responses to thrombin between the two groups. In the combined group of male and female subjects, platelet cytosolic calcium correlated with diastolic blood pressure and mean arterial pressure (r=0J7, p<0.001 and r=032,p<0.01, respectively). Intact parathyroid hormone correlated with systolic and mean arterial blood pressure (r=0.41,p<0.001 for both). Age correlated with both systolic blood pressure (r=0.40, p<0.001) and intact parathyroid hormone (r=0.51, p<0.001). When multiple regression analysis was performed using mean arterial pressure as the dependent variable, platelet cytosolic calcium and intact parathyroid hormone maintained significant correlations with mean arterial pressure. Platelet cytosolic calcium did not correlate with intact parathyroid hormone. These results suggest that both platelet cytosolic calcium and intact parathyroid hormone are associated with blood pressure regulation in normotensive subjects. However, the influences of these two factors on blood pressure are not interrelated. (

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Section: Discussionmentioning

confidence: 99%

Parathyroid hormone, platelet calcium, and blood pressure in normotensive subjects.

Brickman¹,

Nyby²,

Hungen³

et al. 1991

Hypertension

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“…Pang et al 36 were unable to detect an increase in any serum PTH fragments during the development of hypertension in SHR, yet others have shown definite evidence of increased parathyroid gland activity in this same model. 37 In normal humans, chronic administration of PTH increases blood pressure, although this pressor effect could be due to the resultant increase of serum calcium.…”

Section: Discussionmentioning

confidence: 99%

Calcitropic hormones, platelet calcium, and blood pressure in essential hypertension.

et al. 1990

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Plasma ionized calcium, platelet cytosolic calcium (using the fura-2 method in gel-filtered platelets), parathyroid hormone (both the intact hormone and a midmolecule portion), calcitriol, and calcidiol were measured in 19 untreated male patients with essential hypertension and 19 age-matched normotensive male research subjects. Mean levels of platelet cytosolic calcium, parathyroid hormone, calcitriol, and calcidiol were all significantly higher, whereas plasma ionized calcium was significantly lower, in the hypertensive group compared with the normotensive group. Both platelet cytosolic calcium and intact parathryoid hormone were positively correlated with mean arterial pressure (r=0.58, /?<0.001; r=0.S4, p<0.001, respectively), whereas plasma ionized calcium was inversely correlated with mean arterial pressure (r=-0.60, p<0.001) in the combined group of all study subjects. All three of these correlations were significant in the hypertensive group alone but not in the normotensive group alone. When analyzed with plasma ionized calcium, body mass index, serum calcitriol, and calcidiol in a multivariable regression model, the significance of the partial regressions of platelet cytosolic calcium and parathyroid hormone with mean arterial pressure persisted. Intact parathryoid hormone was positively correlated to platelet cytosolic calcium (r=0.43, p<0.01) and plasma ionized calcium was inversely correlated to platelet cytosolic calcium (r= -0.44,p<0.01). These results confirm previous reports of disturbances of calcium metabolism in essential hypertension and suggest that the elevated platelet cytosolic calcium observed in essential hypertension may be linked to one or more of these alterations of calcium metabolism. {Hypertension 1990;16:515-522) S everal studies have described disturbances of calcium metabolism in subjects with essential hypertension. McCarron 1 reported decreased plasma ionized calcium in patients with essential hypertension and also suggested that subjects with essential hypertension include less calcium in their diet.2 Further, McCarron and Morris 3 also found that supplementing the dietary calcium intake of subjects with essential hypertension could decrease the blood pressure of some subjects. The blood pressure-lowering effect of dietary calcium has also been observed in rat models of hypertension.

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“…Extrarenal la-hydroxylase activity has been identified recently in several tissues (4-6, 8, 38, 39 cause injury to the endothelial lining is a key facet of the current theory of the pathogenesis of atherosclerosis, a negative or positive influence of 1,25(OH)2D3 in the reendothelialization process could be of great significance to determining the incidence of atherosclerotic plaque formation. Finally, abnormalities in the levels of calcium regulating hormones such as l,25(QH)2D3 have been recognized in human and experimental hypertension (42,43). Therefore, interactions of 1,25(OH)2D3 with endothelial cells as well as with vascular smooth muscle cells in the control of vascular tone (44)(45)(46) represent potentially exciting areas of investigation that could provide a link between the 1,25(OH)2D3 hormone and the pathophysiology of coronary artery disease.…”

Section: Assay Of Vdr Activitymentioning

confidence: 99%

Identification and regulation of 1,25-dihydroxyvitamin D3 receptor activity and biosynthesis of 1,25-dihydroxyvitamin D3. Studies in cultured bovine aortic endothelial cells and human dermal capillaries.

et al. 1989

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Because 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has been shown to play roles in both proliferation and differentiation of novel target cells, the potential expression of 1,25(OH)2D3 receptor (VDR) activity was investigated in cultured bovine aortic endothelial cells (BAEC). Receptor binding assays performed on nuclear extracts of BAEC revealed a single class of specific, high-affinity VDR that displayed a 4.5-fold increase in maximal ligand binding (Nm.x) in rapidly proliferating BAEC compared with confluent, density-arrested cells. When confluent BAEC were incubated with activators of protein kinase C (PKC), N., increased 2.5-fold within 6-24 h and this upregulation was prevented by sphingosine, an inhibitor of PKC, as well as by actinomycin D or cycloheximide. Immunohistochemical visualization using a specific MAb disclosed nuclear localized VDR in venular and capillary endothelial cells of human skin biopsies, documenting the expression of VDR, in vivo, and validating the BAEC model. Finally, additional experiments indicated that BAEC formed the 1,25(OH)2D3 hormonal metabolite from 25(OH)D3 substrate, in vitro, and growth curves of BAEC maintained in the presence of 10-8 M 1,25(OH)2D3 showed a 36% decrease in saturation density. These data provide evidence for the presence of a vitamin D microendocrine system in endothelial cells, consisting of the VDR and a la-hydroxylase enzyme capable of producing 1,25(OH)2D3. That both components of this system are coordinately regulated, and that BAEC respond to the 1,25(OH)2D3 hormone by modulating growth kinetics, suggests the existence of a vitamin D autocrine loop in endothelium that may play a role in the development and/or functions of this pathophysiologically significant cell population. Introduction It is well established that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)' is a crucial hormone in Ca2' homeostasis (1). (13) and also is biosynthesized in several ofits peripheral target cells (4-6) in addition to the traditional renal site of formation. Because endothelial cells are a dynamic tissue with spontaneous or injury-dependent cell renewal and expression of specific cell functions at the blood/vessel-wall interface, these cells were examined to determine whether they are potential targets for 1,25(OH)2D3. Initially, the possible presence of specific binding sites for 1,25(OH)2D3 was probed using cultured bovine aortic endothelial cells (BAEC) as a model. When receptors for 1,25(OH)2D3 were observed, the following hypotheses were tested: (a) that the growth state of BAEC may be associated with changes in VDR activity; (b) that BAEC differentiation induced by activators of protein kinase C (PKC) (14-17) may be associated with VDR regulation; (c) that growth parameters of BAEC may be altered in response to 1,25(OH)2D3; (d) that the receptor may be expressed in vivo in endothelial cells in venules and capillaries of human skin; and (e) that BAEC may possess la-hydroxylase activity to form the sterol hormone ligand for the receptor. These studies describe the ...

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Hyperparathyroidism and abnormal calcitriol metabolism in the spontaneously hypertensive rat.

Cited by 40 publications

References 40 publications

Parathyroid hormone, platelet calcium, and blood pressure in normotensive subjects.

Parathyroid hormone, platelet calcium, and blood pressure in normotensive subjects.

Calcitropic hormones, platelet calcium, and blood pressure in essential hypertension.

Identification and regulation of 1,25-dihydroxyvitamin D3 receptor activity and biosynthesis of 1,25-dihydroxyvitamin D3. Studies in cultured bovine aortic endothelial cells and human dermal capillaries.

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