NA+ H+ ANTIPORTER ACTIVITY IN PERIPHERAL-BLOOD LYMPHOCYTES OF OBESE AND TYPE-2 DIABETIC-PATIENTS IS INCREASED ONLY IN THE PRESENCE OF ARTERIAL-HYPERTENSION/

The aim of this work is to evaluate whether type 2 diabetes mellitus, obesity and arterial hypertension, three conditions characterized by t he presence of insulin resistance, share some common genetic markers. A potential candidate is the Na+/H+ antiporter, the increased activity of which is considered a marker of essential hypertension. This ion e xchanger seems to be related to the Na+/Li+ countertransport, that is considered a marker of insulin resistance in essential hypertension an d in type 1 diabetes mellitus. In this study we wished to clarify whet her the activity of the Na+/H+ antiporter is increased not only in hyp ertensive subjects, but also in obese and type 2 diabetic patients, bo th in the presence and in the absence of arterial hypertension. The ac tivity of the ion exchanger was measured in peripheral blood lymphocyt es (PBL) by clamping intracellular pH (pH(i)) at 5.8-6.2 and then dete cting the rate of the proton efflux after sodium addition. In the abse nce of arterial hypertension, no significant difference in this parame ter was observed in obese and type 2 diabetic patients in comparison w ith normal subjects. In the presence of arterial hypertension, there w as a significant increase in the Na+-induced H+ efflux at the internal pH (pHi) values of 5.8 and 6.2 both in hypertensive controls and in h ypertensive obese and type 2 diabetic patients (P=0.05-0.0001 vs. norm otensive subjects and patients). In particular, H+ efflux at pH 5.8 (m mol l(-1) min(-1)) was 35.36+/-2.48 in normotensive and 42.77+/-1.63 i n hypertensive control subjects (P=0.045), 33.06+/-1.88 in normotensiv e and 50.40+/-5.21 in hypertensive obese patients (P=0.009), 31.16+/-1 .84 in normotensive and 55.54+/-5.83 in hypertensive type 2 diabetic p atients (P=0.0001). H+ efflux showed a significant correlation with bo th systolic (at pHi 5.8, r=0.473, P=0.001; at pHi 6.2, r=0.357, P=0.01 6) and diastolic blood pressure (at pHi 5.8, r=0.600, P=0.0001; at pHi 6.2, r=0.555, P=0.0001). Therefore, our study demonstrates that the h yperactivity of the Na+/H+ exchanger in peripheral blood lymphocytes i s also a marker of arterial hypertension in obesity and in type 2 diab etes mellitus, and that the exchanger activity is not increased in the se two conditions in the absence of arterial hypertension.