Effects of Aging on Serum Ionized and Cytosolic Free Calcium

Abstract

Abstract-Elevated cytosolic free calcium (Ca i ) and reciprocally reduced, extracellular ionized calcium (Ca-ion) levels are observed in both hypertension and non-insulin-dependent diabetes mellitus (NIDDM). Because the changes of vascular function and insulin sensitivity in these conditions resemble the changes associated with "normal" aging, we wondered to what extent similar alterations in calcium metabolism occur with aging per se in the absence of overt hypertension or diabetes. We therefore measured platelet Ca i levels by spectrofluorometry and serum Ca-ion levels in normotensive, nondiabetic, healthy, normal, elderly (Ͼ65 years old) subjects, mean age ϮSEM, 72.2Ϯ1.5 years old (nϭ11); in healthy, normal, young (Ͻ65 years old) adults, 46.1Ϯ2.3 years old (nϭ12); in 10 young adult hypertensives, 48.6Ϯ1.9 years old; and in 10 normotensive NIDDM subjects, 49.2Ϯ1.6 years old. Platelet Ca i levels were higher (104.5Ϯ4.9 versus 80.2Ϯ1.8 nmol/L, PϽ0.01) and Ca-ion levels lower (1.212Ϯ0.010 versus 1.236Ϯ0.011 mmol/L, PϽ0.05) in normal elderly compared with young control subjects, but normal elderly Ca i and Ca-ion levels were indistinguishable from those in hypertensive (Ca i 107.5Ϯ3.6 nmol/L, Ca-ion 1.210Ϯ0.009 mmol/L) and NIDDM (Ca i 110.7Ϯ4.7 nmol/L, Ca-ion 1.204Ϯ0.014 mmol/L) subjects. In normal subjects, significant correlations were found between platelet Ca i levels and age (rϭ0.655, PϽ0.01) and between Ca i levels and systolic blood pressure (rϭ0.733, PϽ0.001). We conclude that aging is associated with alterations of Ca i and Ca-ion levels resembling those changes present at any age in hypertension and type 2 diabetes. We hypothesize that these alterations of calcium metabolism underlie the predisposition to the alterations of blood pressure and insulin sensitivity characteristic of "normal" aging. The data also suggest that studies of the aging process should be limited to subjects with normal blood pressure and glucose tolerance. Key Words: calcium Ⅲ platelets Ⅲ aging Ⅲ hypertension Ⅲ diabetes mellitus C alcium ions, both intracellular and extracellular, are critically important for a wide spectrum of cellular processes, including skeletal, cardiac, and vascular smooth muscle contraction; neural excitability; and stimulussecretion coupling in all endocrine and exocrine tissues. 1,2 In the steady state, altered calcium and magnesium levels are present in essential hypertension and in non-insulindependent diabetes mellitus (NIDDM). 2 Elevated basal cytosolic free calcium (Ca i ) levels, as well as defective membrane binding and transport kinetics of calcium, have been identified in platelets, 3 erythrocytes, 4 lymphocytes, 5 and adipocytes 6 of hypertensive subjects, in whom blood pressure levels were closely and directly related to Ca i content. 3,4 In diabetes, even in the absence of overt hypertension, Ca i levels were similarly elevated, 4 and defective calcium handling has been found in all diabetic tissues tested thus far, including cardiac and skeletal muscle, arteries, kidney, liver, erythrocytes, o...

Insulin sensitivity increase after calcium supplementation and change in intraplatelet calcium and sodium–hydrogen exchange in hypertensive patients with Type 2 diabetes1

“…Increased [Ca 2+ ] i has been suggested to be a common denominator for the association between Type 2 diabetes, hypertension and obesity [8,29]. Indeed, elevated basal [Ca 2+ ] i levels as well as defective membrane transport kinetics of Ca 2+ have been reported in all cell types in subjects with hypertension as well as in those with diabetes, even in the absence of overt hypertension [8,[30][31][32].…”

KADAR Na+, K+, Cl-, DAN KALSIUM TOTAL SERUM DARAH SERTA HUBUNGANNYA DENGAN TEKANAN DARAH PADA PENDERITA HIPERTENSI

“…Berdasarkan Tabel 6, terlihat bahwa terdapat perbedaan yang signifikan antara kadar Na+ serum pada penderita hipertensi dengan subjek normotensi dimana rata-rata kadar Na+ serum pada hipertensi (146.6±1.8mmol/L) lebih tinggi dibandingkan dengan normotensi (144.3±2.7mmol/L). Hasil penelitian ini sesuai dengan penelitian Barbagallo et al (2000) yang menyebutkan bahwa kadar Na+ serum pada penderita hipertensi lebih tinggi dibandingkan normotensi (141.0±0.4 >140.8±0.4mmol/L). Menurut Kee (1996) dan Chris (2010), kadar Natrium dalam darah normalnya adalah 135-145 mmol/L, dan pada penelitian ini hasil rata-rata kadar Na+ pada serum melampaui batas normal kadar Na+ dalam darah yang ditetapkan.…”

“…Hasil penelitian ini didukung dengan penelitian Barbagallo et al (2000) yang menyebutkan bahwa kadar K+ serum pada penderita hipertensi lebih rendah dibandingkan normotensi (4.1±0.06<4.5±0.07mmol/L). Menurut Sacher (2002), nilai rujukan kadar Kalium dalam darah normalnya adalah 3.5-5.3 mmol/L, dan pada penelitian ini hasil rata-rata kadar K+ baik pada serum penderita hipertensi maupun subjek normotensi masih terdapat diambang batas normal nilai rujukan.…”

Diet and arterial hypertension: Is the sodium ion alone important?

“…54,55 Anomalies in the physical characteristics of the cell membranes and in calcium ions transport systems have been implicated in the pathogenesis of arterial hypertension. 56 On reviewing the enormous body of research on this subject, Swales 57 observes that all the cellular anomalies reported probably occur secondary to changes in sodium transport, so in cases of arterial hypertension, an altered calcium metabolism is due to an increase in the sodium intake.…”