Acta Physiol Scand 1991, 141, 343-350

ADONIS

000167729100052R

Effects of calcium supplementation and deoxycorticosterone on plasma atrial natriuretic peptide and electrolyte excretion in spontaneously hypertensive rats I. P O R S T I , H. WUORELA, P. ARVOLA, P. M A M M I , A.-K. N U R M I , J. K O I S T I N A H O T , P. LAIPPALA" and H. VAPAATALO Department of Biomedical Sciences and Department of Public Health, University of Tampere, Finland H., ARVOLA, P., MAMMI,P., NURMI,A.-K., KOISTINAHO, J., PORSTI,I., WUORELA, LAIPPALA,P. & VAPAATALO, H. 1991. Effects of calcium supplementation and deoxycorticosterone on plasma atrial natriuretic peptide and electrolyte excretion in spontaneously hypertensive rats. Acta Physiol Scund 141, 343-350, Received 20 March 1990, accepted 17 October 1990. ISSN 0001-6772. Department of Biomedical Sciences and Department of Public Health, University of Tampere, Finland. The effects of calcium and the mineralocorticoid deoxycorticosterone (DOC) on blood pressure were studied in four groups of spontaneously hypertensive rats (SHR) : (1) control ; (2) calcium ; ( 3 ) deoxycorticosterone and ; (4) deoxycorticosterone calcium. Calcium was given as 1.5yo calcium chloride in drinking fluid and deoxycorticosterone by weekly subcutaneous injections (25 mg kg-'). During the nine weeks of treatment the increase in systolic blood pressure was enhanced in the deoxycorticosterone and attenuated in the calcium group, whereas the deoxycorticosterone calcium group did not deviate from control. Total plasma calcium was elevated in the calcium group. Plasma concentrations of sodium and atrial natriuretic peptide (ANP) were increased by deoxycorticosterone while neither of the calcium-treated groups differed from control in these respects. Urinary excretions of calcium and sodium were increased in both groups receiving calcium, and also the deoxycorticosterone group excreted more calcium into urine than the control. Adrenergic nerve density in a section of the mesenteric artery and the urinary excretion of noradrenaline and adrenaline were similar in all study groups. The results indicate that calcium supplementation can attenuate the development of hypertension and prevent the deoxycorticosterone-induced blood pressure rise in SHR, possibly by influencing sodium metabolism as seen in increased natriuresis, and by preventing the actions of deoxycorticosterone on sodium balance.

+

+

Key words: ANP, blood pressure, calcium, catecholamines, deoxycorticosterone, SHR, sodium.

During the past few years, a hypothesis has been developed that dietary calcium deficiency is associated with essential hypertension (McCarron 1985). Both clinical (Saito et al. 1989) and experimental (Lau et al. 1984, Furspan et al. 1989) studies suggest that calcium deficiency is Correspondence : Ilkka Porsti, Department of Biomedical Sciences, University of Tampere, P.O. Box 607, SF-33101 Tampere, Finland.

linked to hypertension and that calcium supplementation reduces blood pressure. A high calcium diet also prevents the development of mineralocorticoid hypertension in rats (DiPette et al. 1989). However, contradictory results have been published (Capuccio et al. 1987, Luft et al. 1988). T h e mechanisms underlying the blood pressure-lowering effect of calcium still remain to be elucidated. Bohr & Webb (1984) and Furspan et

343

344 240

I. Porsti et al.

1

220 h

0

I E E u

s

200-

v)

:

T

whether alterations in plasma ANP, electrolyte excretion and the adrenergic system participate in the blood pressure-lowering effect of oral calcium supplementation, and whether renin suppression by the mineralocorticoid deoxycorticosterone (DOC) modifies the antihypertensive action of a high calcium diet.

M A T E R I A L S A N D METHODS

Forty-eight male SHR of the Okamoto-Aoki strain (Mdegaard's Breeding Centre, Ejby, Denmark) were 0 used. Eight-week old animals (weight 200215 g) were JY 180divided into four groups (n = 12) of equal mean 0 .-0 systolic blood pressures (177-178 mmHg). The groups +were: (1) control; ( 2 ) calcium; (3) DOC and; (4) DOC+calcium. The control and DOC animals had 160 tap water as drinking fluid (containing only minimal amounts of electrolytes : sodium 170, potassium 30.6, 0 3 6 9 and calcium 480 pmol I-'), while the calcium and DOC +calcium groups received 1.5 yo calcium chlorTime (weeks) Fig. 1 Systolic blood pressure in the control (O), ide solution. The DOC and DOC calcium rats were calcium (e),DOC (A)and DOCfcalcium (A) injected once a week with deoxycorticosterone trimethylacetate (Percorten M, Ciba-Geigy Ltd., Basle, groups during the 9-week study. Switzerland), 25 mg kg-' s.c., and the control and al. (1989) have suggested that dietary calcium calcium groups received an equal volume of saline. provides a membrane stabilizing effect in vascular The rats were housed in individual cages and had free access to drinking fluid and food pellets (Ewos, smooth muscle, resulting in attenuated smooth Sodertalje, Sweden) containing 11 g kg-' of calcium muscle reactivity. Calcium supplementation has and 7 g kg-' of sodium chloride. The consumption of also been found to enhance natriuresis (Ayachi drinking fluid was measured once a week by weighing 1979), and to decrease sympathetic nerve activity the bottles. in spontaneously hypertensive rats (SHR) (Luft The systolic blood pressures of the unanaesthetized et al. 1988). McCarron et al. (1985) have animals were measured once a week by the tail cuff suggested that increasing dietary sodium am- method at 28 "C (Model 129 Blood Pressure Meter, plifies the hypotensive effect of calcium, and I I T C Inc., Woodland Hills, CA, U.S.A.). During study weeks 1, 6 and 9, urine was collected Resnick et a.1. (1986) found that dietary calcium for 24 h in metabolic cages, where the animals had effectively reduced blood pressure especially in free access to food and drinking fluid. As a preservative sodium-volume-dependent experimental hyperfor catecholamines, 1 ml of 6 mol 1-' hydrochloric tension. acid was added to the urine-collecting bottles during T h e atrial natriuretic peptides (ANP) are week 9. Urine volumes were measured and the peptide hormones with natriuretic and vaso- samples stored at -20 "C until assayed. relaxant properties. ANP participates in the After 9 weeks of study the rats were weighed, control of electrolyte balance and blood pressure decapitated and exsanguinated. The hearts were (Laragh & Atlas 1988). T h e circulating ANP excised and weighed as a whole. Blood samples were concentration is increased by dietary sodium taken into chilled tubes on ice containing aprotinin excess (Sagnella et al. 198S), plasma volume (500 kIU m1-l) and EDTA (2.7 mmol I-') for ANP expansion (Lang et al. 1985) and high blood assays, and heparin (100 U ml-') for electrolyte determinations. Plasma was separated by centripressure (Kohno et al. 1987). fugation (30 min, f 4 "C) and the samples stored at Recently Fujimura et al. (1989) reported that -70 "C until assayed. acute hypercalcaemia is a potent stimulus for ANP was measured by radioimmunoassay from ANP release from the hearts of SHR in the 0.5 ml of plasma (pH adjusted to 3.0 with 2 mol I-' absence of any significant change in blood hydrochloric acid). The samples were extracted with pressure. Amprep C8 columns (Amersham International, BuckThe aim of the present study was toinvestigate inghamshire, England), the columns were washed 0

" I v)

+

+

Calcium, ANP and electrolytes in SHR

345

Table 1. Mean supplemented calcium intake during the study, consumption of drinking fluid and 24-h urine volume and calcium excretion related to urinary creatinine excretion during study weeks 1, 6 and 9 in the control, calcium, DOC and DOC calcium groups (ANOVA for repeated measurements, comparison between groups, mean f SE, n = 12 in each group)

+

Variable

Control

Mean supplemented calcium intake (mg kg-l d-l) Consumption of drinking fluid (ml d-') Week 1 Week 6 Week 9 Urine excretion (ml d-') Week 1 Week 6 Week 9 Urine calcium excretion (pmol pmol-' creatinine d-') Week 1 Week 6 Week 9

-

Calcium

494 f24

DOC

DOC + Calcium

534 k 20

~

ANOVA P value"

0.0787

30.6f 1.2 22.4 f0.8** 35.4+ 1.7 26.3f2.3** 40.1 k 2 . 3 27.5f 1.7"*"

29.7 f0.7 35.6f 1.4 41.6f 1.6

23.5+0.7* 26.7 k 1.9* 34.6+ 1.5"

< 0.0001

14.8f1.3 9.3f0.5"' 16.7f 1.3 12.7k 1.3" 21.9f 1.6 15.5+ 1.1""

13.9f1.2 19.9f 1.3 24.5f 1.3

10.6+0.6+ 13.6f 1.2 20.0f0.8

< 0.0001

2.00 f0.14""" 1.73f0.10*** 1.93f0.10"'""

< 0.0001

0.14f 0.01 1.82 f0.10*** 0.14 f0.02 0.04f0.01 1.29+0.08*** 0.14f0.02*+ 0.08f0.01 1.57 f0.10""" 0.25 f0.02***

* P < 0.05 compared

to control, to control, *** P < 0.001 compared to control. a ANOVA for repeated measurements, comparison between groups.

*" P < 0.01 compared

with 7 ml of 0.1 yo trifluoroacetic acid, and ANP eluted with 4 ml of 60% acetonitrile in 0.1% trifluoroacetic acid. After evaporation with nitrogen the dry residue was dissolved in an assay buffer, and ANP was assayed with a commercial kit (radioimmunoassay for alpha-rat ANP, Peninsula Laboratories, Inc., Belmont, CA, U.S.A.). Sodium, potassium and calcium concentrations in the plasma and urine were analysed by an atomic absorption spectrophotometer (AAS) (Spectr AA-30, Varian, Techtron Ltd., Victoria, Australia). In the calcium samples, lanthanium chloride (final concentration 5 mmol I-') was used as an ionization suppressant. It was prepared by dissolving La,O, (AAS grade, Aldrich, Milwaukee, WI, U.S.A.) in concentrated hydrochloric acid, and by diluting it in deionized water. Urine catecholamines were purified according to Riggin & Kissinger (1977) and measured by HPLC with electrochemical detection (Goldstein et al. 1985). Seven to eight rats from each group were used to measure the densities of adrenergic nerve fibres and the mean wall :lumen ratios in the superior mesenteric

artery. A standard ring segment of the artery was excised and immersed in liquid nitrogen. Fifteen cross-sections at 5 p m thickness, 50 pm apart from each other, were cut with a cryostat (Leitz, Wetzlar, F.R.G.), placed on a gelatin-coated slide and processed according to the sucrose-phosphate-glyoxylic acid histofluorescence method (De la Torre 1980, Koistinaho et al. 1989). The number of fluorescent nerve terminals surrounding each vessel at the adventitia/media border were counted under an Olympus Vanox T fluorescence microscope equipped with a filter set suitable for catecholamine fluorescence. In order to determine wall :lumen ratios, the same sections were stained with toluidine blue and photographed using light microscopy. Wall lumen thickness and lumen diameter were measured as previously described (Pang & Scott 1981). The experimental design was approved by the Animal Experimentation Committee of the University of Tampere. Statistics. Statistical analysis was carried out using one-way analysis of variance (ANOVA), supported by Bonferroni confidence intervals when carrying out

346

I. Porsti et al.

pairwise comparisons between the test groups. Analysis of variance for repeated measurements was applied when the data consisted of repeated observations at successive time points. Comparisons were made between all groups, or between two treatments groups, when appropriate. Unless otherwise indicated, the P values in the text refer to ANOVA for repeated measurements. The results are expressed as meanf SE, and P values 0.05 or less are considered significant.

**

T

RESULTS During the study systolic blood pressure increased in all groups (Fig. 1) the final values being: control 211 + 2 , calcium 201 k3, DOC 235 f1 and DOC calcium 209 f3 mmHg. Only at study weeks eight and nine the mean blood pressure in the calcium group was lower than in the control group ( P < 0.05, Bonferroni test). T h e rise in blood pressure was enhanced in the DOC group when compared to both the

+

4-

3b

1

0

Fig. 3 Plasma concentrations of ANP, sodium, calcium potassium and calcium in the control (m), DOC (m) and DOC+calcium (N) groups at the end of the 9-week study ("P < 0.05 and P < 0.01 compared to control, t P < 0.05 and f t t P < 0.001 compared to DOC, n = 12 in each group, mean & SE).

(o), +"

3or

+

control and the DOC calcium groups (P < 0.001). Treatment with DOC calcium had no influence on blood pressure as compared to the control group. Based on fluid consumption, the mean daily intake of supplementary calcium ranged from 401 to 751 mg kg-' with no difference between the calcium and DOC calcium groups (Table 1). During the study both calcium-supplemented groups drank less than the controls (Table 1). Urine volumes were smaller in the calcium group throughout the study, and in the DOC+ calcium group during week 1 when compared to the control. Both calcium groups excreted much larger amounts of calcium into urine than the controls, and toward the end of the trial calcium excretion was also increased in the DOC group (Table 1).

+

Week 1 Week 6 Week 9 Fig. 2 The 24-h urinary excretions of sodium and potassium related to creatinine excretion during study calcium (m), weeks 1, 6 and 9 in the control (O), DOC (m) and DOC+calcium (R) groups (" P < 0.05 compared to control, t P < 0.05 compared to DOC, n = 12 in each group, meanf SE).

+

347

Calcium, ANP and electrolytes in SHR

Table 2. The final body weight, heart weight related to body weight, the wal1:lumen ratio and the number of adrenergic nerve fibres in the mesenteric artery, and the 24-h urinary excretion of noradrenaline and adrenaline during study week 9 in the control, calcium, DOC and DOC+calcium groups (one-way ANOVA, mean fSE, n = 12 in each group) one-way

Variable

Control

Final body wt (9) Heart: rat wt

Calcium

DOC

DOC + Calcium

347 k 3.9 3.98k0.06

339 5.7 3.96k0.06

352 k6.2 4.67+0.11"*"

346 k 4.0 4.21 kO.10

ANOVA

P value 0.2846 < 0.0001

(g kg -7

Mesenteric artery ( n = 7-8) Wall :lumen ratio (per cent) Number of adrenergic

13.5f1.3

11.9k0.9

15.8k1.3

13.9k0.8

0.1097

87.9k5.7

90.2k7.2

95.0k7.8

86.8 k 6.2

0.8351

nerve fibres per section Noradrenaline excretion (pmol d-l)

7197 k 298

7143 206

7S20+ 893

7317k 556

0.9652

639 f62

803k101

511k59

666k115

0.1755

Adrenaline excretion (pmol d-l)

**" P < 0.001 compared

to control.

During week 1 but not later the 24-h excretion of sodium was increased in both groups receiving calcium when compared to control, and also in the DOC calcium group compared to DOC alone (Fig. 2). The 24-h excretion of potassium was increased in the calcium group during week 9 when compared to the control, and in the DOC calcium group when compared to DOC alone. DOC clearly elevated plasma sodium and ANP concentrations, whereas neither of the calcium-supplemented groups differed from control. Plasma ANP and sodium were lower in the DOC calcium group when compared to DOC alone (Fig. 3). Total plasma calcium was elevated in the calcium group compared to control, and in the DOC+calcium group when compared to DOC alone. Plasma potassium concentrations did not deviate from each other in the different treatment groups. The body wts were similar in all study groups throughout the study (Table 2). The weight of the heart related to body weight was clearly increased in the DOC group, while neither of the calcium-supplemented groups differed from control, which result well corresponds with the indirect blood pressure measurements. There were no differences in the wal1:lumen ratios or

+

+

+

the number of adrenergic nerve fibres in a standard section of the mesenteric artery, or in the urine excretion of noradrenaline and adrenaline between the treatment groups (Table 2 ) .

DISCUSSION In the present study calcium supplementation had a blood pressure-lowering effect, confirming earlier observations in SHR (McCarron et al. 1981, Lau et al. 1984). Treatment with the mineralocorticoid DOC enhanced the development of hypertension during the 9-week study. Combined DOC and calcium treatment had no effect on systolic blood pressure, indicating that a high calcium diet can effectively prevent the blood pressure-increasing effect of DOC in SHR. Resnick et al. (1986) have found that increased dietary calcium has opposite effects in different forms of hypertension, lowering blood pressure in salt-dependent and exacerbating it in renindependent hypertension. However, in the present study renin-suppression with DOC did not amplify but prevented the blood pressurelowering effect of calcium. The dose of DOC used significantly suppresses plasma renin activity in SHR (Parsti et al. 1990).

348

I . Porsti et al.

Several disturbances of calcium metabolism have been described in SHR : enhanced influx of calcium in resistance vessels (Cauvin et al. 1987), depressed ability of smooth muscle membrane to transport calcium (Kwan et al. 1980), and reduced uptake of calcium to vascular microsomes (Bhalla et al. 1978). These changes can lead to elevated cytosolic free calcium, and hence increase vascular reactivity and blood pressure. Increased calcium intake may reverse the membrane permeability and decrease vascular smooth muscle tone, or by some other mechanism correct the disturbances of calcium metabolism and reduce blood pressure (McCarron 1985). A high calcium diet increased the urinary excretion of sodium during the first week of the study. The natriuretic and blood pressurelowering effects of increased calcium intake have previously been shown in SHR by Ayachi (1979), and in hypertensive patients by Lasaridis et al. (1989) and Saito et al. (1989). However, some studies have failed to show any significant natriuretic response to calcium supplementation (Lau et al. 1984, McCarron & Morris 1985). The present data indicate that the time period for the monitoring of sodium excretion notably affects the results obtained, the natriuretic effect being most marked at the beginning of the intervention. The renal excretion of sodium is strongly linked to dietary calcium intake (McCarron et al. 1985), and there is a close association between sodium and calcium excretion in the kidney (Lasaridis et al., 1989). Thus the natriuresis following a high calcium diet is explained by the interdependence of sodium and calcium handling in the proximal tubuli and the loop of Henle (Ullrich et al. 1976, Suki 1979). The augmented potassium excretion observed in the present study is probably a result of increased sodium delivery to the nephron. I n the present study urinary calcium excretion was increased in both calcium-treated groups, but also in the DOC group when compared to the control. This mineralocorticoid-induced hypercalciuria has previously been shown in rats even while on a calcium-free diet (Suki et al. 1968). In mineralocorticoid-treated humans urinary calcium excretion is initially reduced during the sodium retention phase. However, during the sodium escape phase, calcium excretion is significantly increased and appears to be independent of sodium excretion. The mechanism of the hypercalciuria is not clear, but urinary

calcium excretion may be enhanced due to mechanisms related to aldosterone-insensitive sites in the distal nephron (Capuccio et al. 1988). Fujimura et al. (1989) have reported that acute hypercalcexnia induced by i.v. calcium chloride is a potent stimulus for ANP release from the hearts of SHR in the absence of any significant change in blood pressure. In addition, the blood pressure-reducing and natriuretic effects of a chronic high calcium diet in SHR may be mediated by increased ANP levels (Kohno et al. 1989). In the present study, calcium supplementation slightly elevated total plasma calcium, but did not affect plasma sodium and potassium concentrations. DOC-treatment clearly increased plasma sodium, and consecutively doubled plasma ANP concentrations. A high calcium diet alone did not affect plasma ANP and sodium, but prevented the DOCinduced increases these parameters. These results suggest that the blood pressure-lowering and natriuretic effects of a high calcium diet are not mediated by ANP. I n contrast, the present data stress the role of increased dietary calcium per se as a modulator of sodium balance. Both of the calcium supplemznted groups consumed less fluid than the controls, probably because of the salty taste of 1.5% calcium chloride solution. However, plasma electrolytes and ANP were not affected by the high calcium diet, and sodium excretion was not decreased but increased during the first study week. Thus the delayed blood pressure effect of calcium is unlikely to be explained by reduced fluid intake, especially when the weight gain of all the experimental animals was similar during the whole study. A high calcium diet may influence blood pressure by affecting the sympathetic tone. Calcium supplementation has been found to attenuate stress-induced blood pressure responses (Hatton et al. 1987) and to reduce plasma adrenaline levels both at rest and in response to cold stress in SHR (Luft et al. 1988). However, we found no differences either in urinary excretion of catecholamines or adrenergic nerve density of the mesenteric artery between the four treatment groups. The present results do not support the conception that alterations in sympathetic nerve functions are essential for the blood pressure-lowering effect of calcium. In conclusion, the present results indicate that calcium supplementation can attenuate the de-

Calcium, ANP and electrolytes in SHR velopment of hypertension and abolish the DOCinduced increase in blood pressure in S H R possibly by augmenting the urinary excretion of sodium and preventing the actions of DOC on sodium balance.

349

I.J. & KEISER, H.R. 1985. Validity and reliability of liquid chromatography with electrochemical detection for measuring plasma levels of norepinephrine and epinephrine in man. Llfe Sci 28, 467-47 5. HATTON,D.C., HUIE,P.E., MUNTZEL, M.S., METZ, J.A. & MCCARRON, D.A. 1987. Stress-induced This study was supported by the Ida Montin blood pressure responses in SHR: effect of dietary Foundation (I. P.) and the Sigrid JusClius Foundation calcium. A m 3 Physiol 252, R48-RS4. (H. W.), and the Academy of Finland (H. V.). PerKOHNO,M., MURAKAWA, K., YASUNARI, K., KURIcorten M was kindly supplied by Ciba-Geigy Ltd., HARA, N. & TAKEDA, T. 1989. Possible involvement Basle. Switzerland. of atrial natriuretic factor in the antihypertensive action of a high-calcium diet in spontaneously REFERENCES hypertensive and Wistar-Kyoto rats. Metabolism 38, 997-1004. AYACHI, S. 1979. Increased dietary calcium lowers K., MATSUURA, T., MURAKAWA, blood pressure in the spontaneously hypertensive KOHNO,M., TAKAORI, K. & TAKEDA, T. 1987. Circulating atrial natriuretic rat. Metabolism 28, 1234-1238. polypeptide in essential hypertension. Am Heart 3 BHALLA, R.C., WEBB,R.C., RINGH,D., ASHLEY, T. & 113, 1160-1163. BROCK,T . 1978. Calcium fluxes, calcium binding J., WADHWANI, K.C. & RAPOPORT, S.I. and adenosine cyclic 3’-5’-monophosphate depen- KOISTINAHO, 1989. Increased density of perivascular adrenergic dent protein kinase activity in the aorta of sponinnervation in tibia1 and vagus nerves of spontaneously hypertensive and Kyoto-Wistar normotaneously hypertensive rats. 3 Neurosci Res 24, tensive rats. Mol Pharmacol 14, 468477. 424-430. BOHR,D.F. & WEBB,R.C. 1984. Vascular smooth L. & DANIEL,E.E. 1980. muscle function and its changes in hypertension. KWAN,C.Y., BELBECK, Abnormal biochemistry of vascular smooth muscle Am 3 Med 77, 3-16. plasma membrane isolated from hypertensive rats. CAPUCCIO, F.P., NIRMALA, D.M. & MACGREGOR, G.A. Mol Pharrnacol77, 137-140. 1988. Renal handling of calcium and phosphate H., GANTEN, D., LUFT,F.C., during mineralocorticoid administration in normal LANG,R.E., THOLKEN, RUSKOAHO, H. & UNGER,T. 1985. Atrial natriuretic subjects. Nephron 48, 280-283. factor : a circulating hormone stimulated by volume D.R.J., CAPUCCIO, F.P., NIRMALA, D.M., SINGER, loading. Nature 314, 264266. SMITH,S.J., SHORE,A.C. & MACGREGOR, G.A. L.H. & ATLAS,S.A. 1988. Atrial natriuretic 1987. Does oral calcium supplementation lower LARAGH, hormone : a regulator of blood pressure and volume blood pressure? A double-blind study. 3 Hypertens homeostasis. Kidney Znt 34 (Suppl. 25), S64S71. 5, 67-71. .ASARIDIS, A.N., KAISIS, C.N., ZANANIRI, K.I., :AUVIN, c . , HWANG,B.S., YAMAMOTO, M. & VAN A.A. 1989. SYRGANIS, C.D. & TOURKANTONIS, BREEMEN, C. 1987. Effects of dihydropyridines on Increased natriuretic ability and hypotensive effect tension and calcium-45 influx in isolated mesenteric during short-term high calcium intake in essential resistance vessels from spontaneously hypertensive hypertension. Nephron 51, 517-523. and normotensive rats. Am 3 Cardiol 59, 116B,AU, K., CHEN,S. & EBY,B. 1984. Evidence for the 122B. role of PO, deficiency in antihypertensive action of )E LA TORRE, J.C. 1980. An improved approach to high-Ca diet. Am 3 Physiol246, H324H331. histofluorescence using the SPG method for tissue U., MEYER,D., STEINBERG, H., LUFT,F.C., GANTEN, monoamines. 3Neurosci Methods 3, 1-5. D. 1988. DIPETTE, D.J., GREILICH, P.E., KERR,N.E., GRAHAM, GLESS,K.H., UNGER,TH. & GANTEN, Effect of high calcium diet on magnesium, catecholG.A. &HOLLAND, O.B. 1989. Systemic and regional amines, and blood pressure of stroke-prone sponhemodynamic effects of dietary calcium suppletaneously hypertensive rats. Proc SOC Exp Biol Med mentation in mineralocorticoid hypertension. 187, 474-481. Hypertension 13, 77-82. D.A. 1985. Is calcium more important R.W. & KEM, D.C. 1989. MCCARRON, FUJIMURA, A., LOWRY, than sodium in the pathogenesis of essential Calcium infusion increases plasma atrial natriuretic hypertension ? Hypertension 7, 607-627. factor in spontaneously hypertensive rats. HyperMCCARRON, D.A., LUCAS, P.A., SCHNEIDMAN, R.J., tension 14, 98-103. FURSPAN, P.B., RINALDI, G.J., HOFFMAN, K. & BOHR, LACOUR, B. & DRUEKE, T. 1985. Blood pressure D.F. 1989. Dietary calcium and cell membrane development in the spontaneously hypertensive rat abnormality in genetic hypertension. Hypertension after concurrent manipulations of dietary Ca2+and 13, 727-730. Na+. Relation to intestinal Ca2+fluxes.JClin Invest GOLDSTEIN, D.S., FEUERSTEIN, G., Izzo, J.L., KOPIN, 76, 1147-1 154.

350

I. Porsti et al.

MCCARRON, D.A. & MORRIS,C.D. 1985. Blood

RIGGIN, R.M. & KISSINGER, P.T. 1977.Determination

pressure response to oral calcium in persons with mild to moderate hypertension. A n n Intern Med

of catecholamines in urine by reverse phase liquid chromatography with electrochemical detection. Anal Chem 49, 2109-2111.

103, 825-831. MCCARRON, D.A., YUNG,N.N., UGORETZ, B.A. & KRUTZIK, S. 1981.Disturbances of calcium metabolism in the spontaneously hypertensive rat. flypertension 3, (Suppl I); 1162-1167. PANG, S.C. & SCOTT,T.M. 1981.Stereological analysis of the tunica media of the aorta and renal artery during the development of hypertension in the spontaneously hypertensive rat. 3 Anatomy 133,

SAGNELLA, G.A., MARKANDU, N.D., SHORE, A.C. & MACGREGOR, G.A. 1985. Effects of changes in dietary sodium intake and saline infusion on immunoreactive atrial natriuretic peptide in human plasma. Lancet 2, 1208-1211.

SAITO,K., SANO,H., FURUTA, Y. & FUKUZAKI, H. 1989. Effect of oral calcium on blood pressure response in salt-loaded borderline hypertensive

patients. Hypertension 13, 219-226. 513-526. SUKI,W.N. 1979. Calcium transport in the nephron. PORSTI, I., WUORELA, H., ARVOLA, P., SAYNAVALAMMI, A m 3 Physiol 235, Fl-F6. P., NURMI,A.-K., HUHTALA, H., LAIPPALA, P. & R.S., RECTOR, F.C. & VAPAATALO, H. 1990. Effects of calcium and SUKI,W.N.,SCHWETTMANN, SELDIN, D.W. 1968. Effect of chronic rnineralodeoxycorticosterone on blood pressure, plasma

corticoid administration on calcium excretion in the rat. Am 3 Physiol 215, 71-74. ULLRICH,K.J., RUMRICH, G. & KLOSS, S. 1976. RESNICK, L.M., SOSA,R.E., CORBETT, M.L., GERTNER, Active Ca2+reabsorption in the proximal tubule of the rat kidney: Dependence on sodium and buffer J.H. 1986. Effect of J.M., SEALEY, J.E. & LARAGH, transport. PJugers Arch 364, 223-228. dietary calcium on sodium volume vs. renindependent forms of experimental hypertension. Trans Assoc A m Pkysicians 99, 172-179. renin activity and vascular reactivity in spontaneously hypertensive rats. Clin Exp Hypertens, par[ A A12, 1159-1174.

Effects of calcium supplementation and deoxycorticosterone on plasma atrial natriuretic peptide and electrolyte excretion in spontaneously hypertensive rats.

The effects of calcium and the mineralocorticoid deoxycorticosterone (DOC) on blood pressure were studied in four groups of spontaneously hypertensive...
590KB Sizes 0 Downloads 0 Views