Vitamin D receptors in heart: Effects on atrial natiuretic factor

We report that receptors for vitamin D exist in distinct regions of the heart in female and male mice, predominantly in the right atrium where most of the cardial atrial natriuretic peptide (ANF) is produced. Tritiated 1,25-dihydroxyvitamin D₃ (1,25-D₃, vitamin D, soltriol) and ANF are colocalized in nuclei and cytoplasm respectively in identical cardiomyocytes. Changes of ANF tissue and blood levels under dietary deficiency and treatment with 1,25-D₃ suggest direct genomic actions of vitamin D on myoendocrine cells of the atrium for the regulation of ANF manufacture and secretion. These results were obtained by combining thaw-mount autoradiography with immunocytochemistry using tritiated 1,25-D₃ and an antibody against rat ANF. This antibody was also used in a radioimmunoassay to determine atrial natriuretic factor in plasma, atria and ventricles of normal or vitamin D-deficient mice.     

Atrial natriuretic factor in hypovolemic tachycardia

Atrial natriuretic factor (ANF) is released in response to many stimuli which increase right atrial pressure. Following hemorrhage pigs lowered their atrial pressures, developed a tachycardia and increased ANF levels. Electrical pacing increased heart rate and ANF levels. There is a stimulus to ANF release other than atrial stretch, probably heart rate.     

Atrial natriuretic factor in hypovolemic tachycardia

Summary Atrial natriuretic factor (ANF) is released in response to many stimuli which increase right atrial pressure. Following hemorrhage pigs lowered their atrial pressures, developed a tachycardia and increased ANF levels. Electrical pacing increased heart rate and ANF levels. There is a stimulus to ANF release other than atrial stretch, probably heart rate.     

Influence of sodium balance on atrial natriuretic factor in rats with one-kidney,one-clip renal hypertension

Summary The influence of sodium intake on the gene expression and circulating levels of atrial natriuretic factor (ANF) was investigated in unanesthetized rats with one-kidney, one-clip renal hypertension. After clipping, the rats were maintained for 3 weeks either on a salt-deficient (n=11) or a regular-sodium diet (n=10). Animals which had received the regular-sodium diet exhibited significantly higher ANF mRNA levels in their right and left atria than salt-restricted animals, whereas there was no significant difference in plasma ANF levels.     

Influence of sodium balance on atrial natriuretic factor in rats with one-kidney, one-clip renal hypertension

The influence of sodium intake on the gene expression and circulating levels of atrial natriuretic factor (ANF) was investigated in unanesthetized rats with one-kidney, one-clip renal hypertension. After clipping, the rats were maintained for 3 weeks either on a salt-deficient (n = 11) or a regular-sodium diet (n = 10). Animals which had received the regular-sodium diet exhibited significantly higher ANF mRNA levels in their right and left atria than salt-restricted animals, whereas there was no significant difference in plasma ANF levels.     

Distribution of the 1,25 dihydroxy-vitamin D3 receptor in the bursa of Fabricius of chicken.

The vitamin D3 metabolite 1,25(OH)2D3 is probably involved in B lymphocyte ontogeny. We therefore determined the distribution of the 1,25(OH)2D3 receptor in the bursa of Fabricius and spleen cells of 7-day-old chicks, by immunohistochemistry using a monoclonal antibody against the chick intestinal cell 1,25(OH)2D3 receptor. The bursa cells of young (7-day-old) chicks contained large amounts of receptor while the spleen cells did not. The bursa cells of older (35-day-old) chicks contained fewer receptors, but the number of receptors in the spleen increased.     

Responses of monkey, rabbit and dog internal carotid arteries to atrial natriuretic factor

Effects of atrial natriuretic factor (ANF) on monkey, rabbit and dog internal carotid arteries were investigated. ANF caused a concentration-dependent relaxation in arterial strips submaximally precontracted with noradrenaline, 5-hydroxytryptamine, or high-potassium solution (10-30 mM). The response was greatest in the monkey arteries and least in the dog arteries. These results suggest that there is a marked species difference in the ANF-induced relaxation of the internal carotid arteries.     

Responses of monkey,rabbit and dog internal carotid arteries to atrial natriuretic factor

Summary Effects of atrial natriuretic factor (ANF) on monkey, rabbit and dog internal carotid arteries were investigated. ANF caused a concentration-dependent relaxation in arterial strips submaximally precontracted with noradrenaline, 5-hydroxytryptamine, or high-potassium solution (10–30 mM). The response was greatest in the monkey arteries and least in the dog arteries. These results suggest that there is a marked species difference in the ANF-induced relaxation of the internal carotid arteries.     

Distribution of the 1,25 dihydroxy-vitamin D3 receptor in the bursa of Fabricius of chicken

The vitamin D₃ metabolite 1,25(OH)₂D₃ is probably involved in B lymphocyte ontogeny. We therefore determined the distribution of the 1,25(OH)₂D₃ receptor in the bursa of Fabricius and spleen cells of 7-day-old chicks, by immunohistochemistry using a monoclonal antibody against the chick intestinal cell 1,25(OH)₂D₃ receptor. The bursa cells of young (7-day-old) chicks contained large amounts of receptor while the spleen cells did not. The bursa cells of older (35-day-old) chicks contained fewer receptors, but the number of receptors in the spleen increased.     

Lack of influence of vitamin D deficiency on insulin release from the isolated pancreatic islets of rats

Pancreatic islets were isolated from young (100 g) and adult (390 g), normal and vitamin D deficient male Sprague-Dawley rats. The release of insulin from leucine-stimulated or glucose-stimulated islet was not altered by vitamin D deficiency. The in vitro addition of either 25-hydroxy- or 1,25-dihydroxyvitamin-D had no effect on insulin release from either normal or vitamin D deficient islets. We conclude that the earlier report (Normal et al., Science 209 (1980) 823-825) on vitamin D deficiency depressing insulin secretion from the perfused pancreas must be related to the vitamin's effect on insulin synthesis and not the islet's release of insulin.     

The action of various vitamin D3 metabolites on calcium and phosphorus metabolism in chick embryo calvariae

Chick embryos from vitamin D-deficient hens given physiological doses of 1,25-dihydroxyvitamin D3 or 24,25-dihydroxyvitamin D3 or both become severely hypocalcemic, hyperphosphatemic and fail to hatch as compared to those derived from hens given 25-hydroxyvitamin D3 or 24,25-difluoro-25-hydroxyvitamin D3. Calvariae from the former contain less mineral and on incubation in vitro produce significantly lower calcium and higher phosphate concentration in the medium than do the calvariae derived from the embryos of hens supported on 25-hydroxyvitamin D3 or 24,24-difluoro-25-hydroxyvitamin D3.     

Drug susceptibility of PCA in WBB6F1-W/Wv mice

Our previous study revealed that passive cutaneous anaphylaxis (PCA) can be produced in congenitally mast cell-deficient WBB6F1-W/W^v (abbreviated as W/W^v) mice on sensitization with undiluted or slightly diluted allogeneic and xenogeneic antisera but not on sensitization with allogeneic monoclonal immunoglobulin (Ig)E and IgG1 antibodies regardless of the antibody concentration [1]. In view of these findings, the present study was conducted to characterize PCA in this strain from its drug susceptibilities using mast cell-bearing WBB6F1-+/+ (abbreviated as +/+) and B6D2F1 mice as references. PCA in W/W^v mice mediated by a low dilution (1  4) of hyperimmune serum to bovine serum albumin of the B6D2F1 mouse origin was markedly suppressed by CV-6209, an antagonist of platelet-activating factor (PAF), but not by antihistamines such as cyproheptadine and oxatomide. In contrast, PCA in +/+ and B6D2F1 mice mediated by a high dilution (1  128) of the anti-serum (virtually by IgG1 antibody) was nearly completely suppressed by antihistamines but not by CV-6209. A remarkable difference between PCA in W/W^v and reference mice was also observed in the susceptibility to monoclonal anti mouse granulocyte (Gr-1) antibody PCA in W/W^v mice was potently suppressed by the 1- to 3-day pretreatment with this antibody but that in references was not at all. Putting these present results together with the previous finding that anti-granulocyte antibody greatly reduces circulatory Gr-1⁺ leukocytes, 1 to 3 days after the treatment [2], it is highly probable that PCA in W/W^v mice mediated by some antibody isotypes other than IgE and IgG1 is produced by PAF mainly released from Gr-1⁺ cells, while IgG1 antibody-mediated PCA in mast cell-bearing reference mice is evoked by histamine derived from mast cells. PCA homologous to that in W/W^v mice could also be produced in the reference mice on sensitization with undiluted or slightly diluted antiserum, when generalized blueing due to excess IgG1 antibody was removed by the oxatomide treatment be fore the antigen challenge. Received 10 December 1997; received after revision 2 February 1998; accepted 23 February 1998     

Developmental actions of natriuretic peptides in the brain and skeleton

The concept that atrial natriuretic peptide (ANP) and the closely related peptides BNP and CNP might be involved in the ontogeny of several organ systems emerged in the late 1980s. While many of the reported in vitro actions have not been examined in the context of organ development in vivo, recent studies demonstrate that mice which lack or overexpress natriuretic peptides or receptors exhibit pronounced skeletal growth defects. This article discusses how natriuretic peptides and other factors appear to regulate bone growth as an example of how natriuretic peptides might participate in the ontogeny of other organ systems. Evidence indicating that natriuretic peptides regulate neural development is then reviewed. Natriuretic peptides and receptors exhibit complex expression patterns in the developing nervous system, where they have been shown to act on neural cells as early as at the embryonic neural tube stage. Interestingly, both bone and brain growth appear to utilize primarily CNP and the CNP-specific type B receptor, and perhaps the type C receptor. In vitro data indicate that CNP may act on developing neurons, astrocytes and Schwann cells like a classical growth factor, regulating proliferation, patterning, phenotypic specification, survival and axonal pathfinding. Natriuretic peptides might also have roles in the vascularization of the embryonic brain, establishment of the blood-brain and blood-nerve barriers, and perhaps in nerve regeneration.Received 13 April 2004; received after revision 20 May 2004; accepted 27 May 2004     

Vitamin C and the immune response.

The inclusion of vitamin C in the drinking water of BALB/c mice was without effect on the humoral antibody response to sheep red blood cells and bacterial lipopolysaccharide. However, there was a significantly increased cell-mediated immune response as determined by increased T-lymphocyte responses to concanavalin A. This might suggest a mechanism, along with interferon enhancement, for the possible protection by vitamin C against some viral infections.     

Vitamin C and the immune response

Summary The inclusion of vitamin C in the drinking water of BALB/c mice was without effect on the humoral antibody response to sheep red blood cells and bacterial lipopolysaccharide. However, there was a significantly increased cell-mediated immune response as determined by increased T-lymphocyte responses to concanavalin A. This might suggest a mechanism, along with interferon enhancement, for the possible protection by vitamin C against some viral infections.We thank Miss Wendy Treat for excellent technical assistance.     

Trichinella spiralis: acceleration and inhibition of cyst calcification in rats.

Daily administration of vitamin D3 (75,000 IU/kg b. wt) for 7 days accelerated Trichinella spiralis cyst calcification in rats with a 14-week-old infection. When disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDP) was administered (50 mg/kg b. wt) from 2 days before until 2 days after vitamin D3 treatment, cyst calcification was inhibited. Thus, the ability to inhibit E. spiralis calcification has demonstrated for the first time.     

Evidence of a subsidiary atrial pacemaker in the crista terminalis of the rabbit heart

Summary The crista terminalis (CT) with musculi pectinati was isolated from the right atrium: it discharged at a frequency intermediate to that of the 2 nodes. Pacemaker action potentials were recorded from the CT deep layer fibers. The results suggest the presence of a subsidiary atrial pacemaker in the CT deep layer.     

Relationship of specific granules to the natriuretic and diuretic activity of rat atria

Summary The isolation of several fractions from rat atrial homogenates, by the use of differential and sucrose gradient centrifugation, indicates that the diuretic and natriuretic activity is restricted to the fractions rich in specific granules. Our preliminary results suggest that the active substance is a small peptide which is probably different from the natriuretic substance(s) already known.Supported by a group grant given by the Medical Research Council of Canada to the Multidisciplinary Research Group on Hypertension of the Clinical Research Institute of Montreal.Acknowledgments. The authors thank Suzanne Diebold for technical assistance.     

Vitamin D3 sulfoconjugate distribution and evolution in pregnant or lactating rats]

24 hrs after intravenous injection of vitamin D3 35S sulfoconjugate the radioactivity in kidney is about twice as much in pregnant Rats as in lactating Rats. It decreases from 24 to 48 hrs in pregnant but increases in lactating Rats kidneys. Hydrolysis of vitamin 3H D3 sulfate is detected in kidney and liver extracts, the ratio of free vitamin D3 on vitamin D3 sulfate is higher in pregnant than in lactating animals. Mammary glands of lactating Rats contain mainly the unchanged vitamin D3 sulfate which can be hydrolysed by new born suckling pups.