The Effect of High Calcium Intake on Intracellular Free [Ca2+] and Na+-H+ Exchange in DOC-NaCl-Hypertensive Rats

Abstract: The effects of calcium supplementation on blood pressure, intracellular free calcium concentration ([Ca²⁺],) and rate of Na⁺-H⁺ exchange were studied in DOC-NaCl-hypertensive rats. All the animals were uninephrectomized and divided into two main groups: the first group received deoxycorticosterone (DOC) (25 mg/kg, s.c.) once a week and had 0.7% NaCl as drinking fluid while the other received equal volumes of saline and tap water to drink. The animals were further divided according to dietary calcium intake: in the Control and DOC groups the chow contained 1.1% calcium, in the Calcium and DOC + Calcium groups, 2.5%. After 6 and 8 weeks, blood pressure in the DOC group was higher than in the Control group; on the other hand, the development of hypertension was attenuated in the DOC + Calcium compared with the DOC group. The Control and Calcium groups did not differ from each other. Platelets and lymphocytes were used as experimental models to study changes in the regulation of [Ca²⁺]ⁱ, evaluated by fluorescent indicators indo-1 and quin-2. In lymphocytes, basal [Ca²⁺]_i was highest in the DOC group, but similar in DOC + Calcium and Control groups. In platelets, both basal and thrombin-stimulated [Ca²⁺]_i were higher in the DOC and DOC + Calcium groups than in the Control group. In both cell types [Ca²⁺]_i was similar in Control and Calcium groups. In addition, platelets were used to study the ability of the cells to recover from intracellular acidification by first blocking the Na⁺ -H⁺ exchange in a Na⁺-free medium and then restarting the exchange mechanism by increasing the extracellular Na⁺ concentration at constant speed. Changes in [pH]_i were monitored by fluorescent indicator BCECF. The rate of Na⁺-H⁺ exchange in the recovery phase did not reveal differences between the experimental groups. Vascular smooth muscle function was examined by determining concentration-response curves for noradrenaline in mesenteric arterial rings and a shift to the left was observed in the DOC and DOC + Calcium groups compared with the Control group. The present data indicate that high calcium intake attenuates the development of mineralocorticoid-salt hypertension. The DOC-induced elevation of blood pressure is associated with higher [Ca²⁺]_i in platelets and lymphocytes, evidencing disturbances in cellular calcium handling. However, possibly due to differing characteristics in regulatory mechanisms between these cell types, supplementary calcium reduced [Ca²⁺]_i only in lymphocytes. The assumed elevation in intracellular sodium did not cause detectable changes in the Na⁺-H⁺ exchange rate in platelets. Enhanced vascular responses to noradrenaline observed in the DOC group were not altered by high calcium intake.