Phosphoinositide Metabolism in Hypertension

Abstract

In essential hypertension, an increase in peripheral resistance is associated with hypertrophy/hyperplasia of smooth muscle cells of the media as well with cell hypercontractility. As a result, the wall-to-lumen ratio decreases and both the basal tone and the response to vasoconstrictor agents increase. To gain insight into the pathogenesis of hypertension, the mechanisms underlying both the smooth muscle hypertrophy and the enhanced reactivity of these cells to vasoactive agents have been investigated. There is ample evidence that free cytosolic calcium plays an important role in the development of tension in vascular smooth muscle. An altered cell calcium homeostasis, which can be involved in the cellular hyperresponsiveness and hyperproliferation, has been reported in various cell types of patients with essential hypertension and of rats with genetic or experimental hypertension (reviewed in [1]). Recently it has been demonstrated that agonists or hormones that elicit physiological responses within cells by modifying the internal free calcium concentration exert their action by activating, through specific enzymes, the metabolism of inositol-containing phospholipds [2]. These phospholipids, also called phosphoinositides, include phosphatidylinositol, phosphatidylinositol 4-phosphate, and phosphatidylinositol 4,5-bisphosphate (PI-P₂). Thus, the metabolism of phosphoinositides, acting as a signaling system, has been investigated in various cell types and in various models of experimental hypertension; reviews on this topic have been already published [3,4]. The scope of this paper is therefore to summarize and to update the results so far obtained and to examine how such a lipid metabolism can be involved in the development of hypertension.