RESUMO
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 micromol/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.