Phospholipase C activity is enhanced in skin fibroblasts obtained from patients with essential hypertension

Objectives In human hypertension, the response of phospholipase C (PLC) to stimuli is enhanced in signal transduction where receptors are coupled to pertussis toxin-sensitive G protein. We investigated PLC activity and its role in human hypertension. Methods and results Skin fibroblasts were cultured from 15 normotensives subjects (53 +/- 4 years, four men and 11 women) and 19 essential hypertension (EH) patients (58 +/- 2 years, nine men and 10 women). Plasma membrane PLC activity, assessed by conversion of the tritiated exogenous phosphatidylinositol-4,5-bisphosphate to inositol trisphosphate, was greater in EH patients than in normotensive subjects (1.4 +/- 0.2 versus 0.7 +/- 0.1 pmol/mg protein/min, P<0.05). There was a positive correlation between PLC activity and mean blood pressure measured at admission and 7 days after admission (r = 0.47 and 0.37 respectively, both P<0.05). The value of the Michaelis constant was lower in EH patients than in normotensive subjects (32.1 +/- 5.6 versus 58.3 +/- 10.0 mumol/l, P < 0.05), despite the fact that maximal velocity of the reaction was no different. Western blot analysis against PLC beta2 and beta3, gamma, delta1, and G protein gamma2 and gamma5 revealed that most PLC and G protein isoforms detected were delta1 of PLC and gamma2 of G protein, and no difference was detected in their amount between two groups. Conclusions We conclude that enhanced PLC delta1 activity may be involved in the pathogenesis of human hypertension. (C) 2003 Lippincott Williams Wilkins.