The Role of Calcium on the Mechanism of Essential Hypertension : with Special Reference to Plasma Ionized Calcium and Renal Calcium Handling

This study was aimed to clarify the role of calcium in the mechanisms of essential hypertension. Sixty-four patients with essential hypertension (EHT) and 38 normotensives (NT) participated in the present study. Under a standard diet including 120 mEq of Na, 75 mEq of K and 600mg of Ca/day, hemodynamics, renal sodium and calcium balance, plasma ionized calcium (pCa2+), plasma parathyroid hormone (PTH) and plasma volume (PV) were measured. Furthermore, nifedipine (Nif) or nisoldipine (Nis) were administered in 9 EHT and 8 EHT respectively, and the above mentioned parameters were also checked. pCa2+ was negatively correlated with mean arterial pressure (MAP) and positively with plasma renin activity (PRA) in EHT. PCa2+ was significantly lower in low renin EHT (LRH) than that in NT and normal renin EHT (NRH). PTH was negatively correlated with pCa2+ and PRA in EHT but not in NT. PTH was significantly higher in LRH than in NT and NRH. Fractional excretion of calcium (FECa) was the same in LRH and NT but significantly lower in these two groups than in NRH. Neither MAP nor creatinine clearance (CCr) showed any significant difference between LRH and NRH. There were no differences in intravascular ionized calcium volume (PV×pCa2+) between NT and LRH, but it was significantly higher in these two groups than in NRH. After a single or 4 weeks administration of Nif or Nis, MAP decreased significantly. Heart rate (HR) increased after a single administration of Ca antagonists and subsequently returned to the baseline level at the 4th week. Urinary excretion of calcium (UCa V), sodium (UNa V), FECa and fractional excretion of sodium (FENa) increased significantly after a single administration of Nif. Although UNa V and FENa returned to the baseline level, UCa V and FECa maintained significantly higher levels for 4 weeks of Nif administration. The change in UCa V was positively correlated with the change in UNa V after a single administration of Nif, while this positive correlation was not observed during chronic administration. PCa2+ did not change throughout the administration period of Nif or Nis, however PTH decreased at the 1st and 4th week. Percent change in MAP correlated negatively with the change in UCa V at the 4th week of Nif administration. These results suggest that renal calcium excretion was attenuated in EHT, particularly in LRH, resulting in an increase of intravascular ionized calcium volume. It was speculated that plasma ionized calcium was shifted into the intracellular space, which may have contributed partially to the low pCa2+ level in LRH. On the other hand, it was also suggested that the decrease of intravascular calcium volume associated with the increase of urinary calcium excretion produced by the treatment ?with Nif or Nis may have played an important role in one of hypotensive mechanisms of Ca antagonists in EHT. Thus, an increase of ionized calcium volume in intravascular space may play an important role in the maintenance of high blood pressure in essential hypertension