Erythrocyte membrane Ca2+-Mg2+ATPase activity in essential and genetic hypertension.
thesisposted on 19.11.2015, 08:51 by Susan Abimbola. Adeoya-Osiguwa
Erythrocyte membrane Ca2+-Mg2+ATPase activity was studied in patients presenting with essential hypertension and their normotensive controls, together with spontaneously hypertensive rat (SHR) and Wistar-Kyoto normotensive control rats (WKYN). Ca2+-Mg2+ATPase activity was determined in inside-out vesicles (45Ca2+ uptake) and ghost membranes (?-32P]ATP hydrolysis) prepared from the same blood sample, in both species, in the absence (basal activity) and presence of calmodulin (calmodulin-stimulated activity). Comparison of the Ca2+-Mg2+ATPase activities showed that there were significant reductions in the enzyme activities of membranes derived from both species of hypertensive subjects, in both the absence and presence of calmodulin. Detergent solubilisation of ghost membrane protein resulted in an elevated Ca2+- Mg2+ATPase activity in soluble extracts obtained from hypertensive and normotensive subjects of both species. Moreover, the reduction in Ca2+- Mg2+ATPase activity, observed in membranes prepared from hypertensive subjects was no longer apparent in the soluble extracts from these subjects when compared with those of their normotensive controls. Furthermore, investigation of the affinity of Ca2+-Mg2+ATPase for calmodulin and free Ca2+ ions showed that in membranes prepared from erythrocytes of patients presenting with essential hypertension and SHR, there were no marked differences in the dependence of the enzyme for either calmodulin or Ca2+ when compared with those of their normotensive controls. Investigations into the effect of temperature on Ca2+-Mg2+ATPase activity and the reconstitution of purified enzyme into a controlled membrane environment has provided evidence which further suggested that the reduced erythrocyte membrane Ca2+-Mg2+ATPase activity in hypertension could result from an altered membrane environment, as opposed to an altered protein function due to altered structure. Therefore, these findings support the hypothesis that a reduced Ca2+- Mg2+ATPase activity could contribute to an elevated [Ca2+]i and thus play a role in blood pressure development.