NA+ H+ EXCHANGE IN HYPERTENSION AND IN DIABETES-MELLITUS - FACTS AND HYPOTHESES/

An enhancement of Na+/H+ exchange (NHE) in blood cells of selected pat ients with essential hypertension and with diabetic nephropathy has be en described by various investigators. Recent studies have shown that enhanced NHE activity persists in immortalized lymphoblasts from these patients after prolonged cell culture and, thus, appears to be under genetic control. Available evidence strongly argues against a mutation in the encoding gene or an overexpression of the NHE. Immortalized ce lls from hypertensive patients with enhanced NHE activity display two- fold enhanced agonist-induced rises of the cytosolic free Ca2+ concent ration and the underlying reason was identified as an increased activa tion of pertussis toxin (PTX)-sensitive G proteins. The molecular mech anism(s) of this phenomenon have not yet been elucidated. It appears l ikely that similar changes contribute to the enhanced NHE activity phe notype in diabetic nephropathy, although experimental evidence for thi s is still lacking. An enhanced activation of PTX-sensitive G proteins could explain many of the hitherto unexplained phenomena in essential hypertension, e.g. inheritance, increased vasoconstriction, hypertrop hy or remodeling of arterial blood vessels and the heart, enhanced pla telet aggregation etc. In diabetes the same defect could provide the b asis for the susceptibility to nephropathy, e.g. by enhancing the dele terious effects of autocrine and paracrine growth factors. Thus, the e xperimental approach of immortalizing blood cells from patients with e ssential hypertension and diabetic nephropathy has opened new horizons in the identification of genetically fixed abnomalities in intracellu lar signal transduction which could contribute to both pathologies and which can now be studied without the confounding influences of the di abetic or hypertensive in vivo milieu.