Increased calcium and decreased magnesium concentrations and an increased calcium/magnesium ratio in spontaneously hypertensive rats versus Wistar-Kyoto rats: relation to arteriosclerosis.
Alterations in the metabolism of calcium and magnesium have been implicated in the pathogenesis of primary hypertension. Calcium influx across the external cellular membrane in smooth muscle cells and cardiomyocytes plays a crucial role in the control of cellular excitation contraction and impulse propagation. Intracellular calcium and magnesium concentrations are controlled by reversible binding to specific calcium-binding proteins. The calcium and magnesium flux across the external membrane is regulated by a calcium pump (calcium-magnesium-ATPase), calcium channels, and binding to the membrane. In cell membranes and in lymphocytes of essential hypertensives our group showed increased calcium and a decreased magnesium and increased calcium/magnesium ratio in hypertensive cells. In this context, in aortic smooth muscle cells from 13 spontaneously hypertensive rats (SHR) of the Münster strain (systolic blood pressure 188.4 +/- 9.8 mm Hg) and 13 normotensive rats (NT, systolic blood pressure 118.5 +/- 7.2 mm Hg) aged 9 months, the intracellular calcium and magnesium contents were measured under nearly in vivo conditions by electron probe microanalysis. Measurements were performed in aortic cryosections 3 microm thick; the calcium content was 124.7 +/- 4.5 mmol/kg dry weight in SHR versus 110.3 +/- 4.1 mmol/kg dry weight in NT (mean +/- SD, P <.01 for both), the magnesium content was 35.5 +/- 3.9 in SHR versus 50.1 +/- 4.9 mmol/kg dry weight in NT (P <.01 for both). The calcium/magnesium ratio was significantly increased in SHR versus NT (3.56 +/- 3.9 versus 2.23 +/- 0.27 [P <.01 for both]). Thus, aortic smooth muscle cells from SHR are characterized by a markedly elevated intracellular calcium and decreased intracellular magnesium contents compared with normotensive cells. Cellular calcium and magnesium handling is disturbed in SHR aortic smooth muscle cells as it is in hypertensive blood cells. The increased calcium/magnesium ratio in hypertensive cells is a pathogenetic factor for the development of arteriosclerosis and hypertension.
Kisters
Klaus
K
Med. Clinic l, St. Anna-Hospital, Herne, Germany. prof.kisters@t-online.de
Wessels
Franz
F
Küper
Heinz
H
Tokmak
Faruk
F
Krefting
Ernst Rudolf
ER
Gremmler
Bernhard
B
Kosch
Markus
M
Barenbrock
Michael
M
Hausberg
Martin
M
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001161:Arteriosclerosis / Q000150:complications / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D004195:Disease Models, Animal; D004577:Electron Probe Microanalysis; D006973:Hypertension / Q000150:complications / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D008274:Magnesium; D002118:Calcium