Intracellular calcium concentration and activation of the Na+/H+ exchanger in essential hypertension.

Abstract

To investigate the relationship between changes in intracellular calcium concentration ([Ca2+]i) and agonist-induced activation of the Na+/H+ exchanger in essential hypertension (EH), platelet [Ca2+]i and pHi were measured in 24 patients with EH (14 males) aged 48 +/- 2 years and 23 matched normotensive controls (NT) (12 males) aged 45 +/- 3 years. Measurements were done with spectrofluorimetry using the dyes Fura-2 for [Ca2+]i and BCECF for pHi. [Ca2+]i and pHi were measured in the resting condition and after stimulation in vitro with 0.1 U/ml human thrombin. The thrombin-induced rise in pHi was Na+ dependent and amiloride sensitive, indicating that it was mediated by the Na+/H+ exchanger. Unstimulated [Ca2+]i was higher in patients with EH than in NT (60 +/- 3 vs. 48 +/- 1 nmol/liter, P < 0.005), but there were no differences in resting pHi between both groups (7.16 +/- 0.01 vs. 7.16 +/- 0.008). In the presence of 1 mmol/liter external calcium (Ca2+o), thrombin-induced increment in [Ca2+]i was significantly greater in patients with EH than in NT (281 +/- 21 vs. 206 +/- 19; P < 0.05) as was the pHi increment (EH: 0.137 +/- 0.01; NT: 0.095 +/- 0.01; P < 0.05). Both agonist-induced increments in [Ca2+]i and in pHi were correlated with mean arterial pressure (MAP) only in the EH group (r = 0.58, P < 0.005 and r = 0.59, P < 0.005, respectively). The agonist-induced rise in pHi was positively correlated with the rise in [Ca2+]i both in the EH group (r = 0.65, P < 0.001) and in the NT (r = 0.55, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)