Phosphoinositide Metabolism in Hypertension
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 ). 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 . 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.
KeywordsVascular Smooth Muscle Cell Essential Hypertension Myosin Light Chain Kinase Primary Hypertension Experimental Hypertension
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- 4.Marche P (1989) Membrane phosphoinositide metabolism in hypertension. News Physiol Sci 4: 230–233Google Scholar
- 7.Shearman MS, Sekuguchi K, Nishizuka Y. Modulation of ion channel activity: a key function of the protein kinase C enzyme family. Pharmacol Rev 41: 212–235Google Scholar
- 9.Whitman M, Cantley L (1988) Phosphoinositide metabolism and the control of cell proliferation. Biochim Biophys Acta 948: 327–344Google Scholar
- 12.Erne P, Resink TJ, Bürgin M, Bürgisser E, Bühler FR (1985) Platelets and hypertension. J Cardiovasc Pharmacol 7 [Suppl 61: 5103 - S108Google Scholar
- 14.Marche P, Koutouzov S, Girard A, Barbier P, Meyer P (1989) Hyperresponsiveness of platelet phospholipase C in essential hypertension. J Vasc Med Biol 1: 137–141Google Scholar
- 18.Livne A, Balfe JW, Veitch R, Marquez-Julio A, Grinstein S, Rothstein A (1987) Increased platelet Na+/H+ exchange rates in essential hypertension: application of a novel test. Lancet i: 533–536Google Scholar
- 19.Ueahra Y, Ishii M, Ishimitsu T, Sugimoto T (1988) Enhanced phospholipase C activity in the vascular wall of spontaneously hypertensive rats. Hypertension 11: 515–524Google Scholar
- 22.Zhu DL, Durant S, Marche P (1990) Phospholipase C activity in cultured aortic fibrobalsts of hypertensive and normotensive rats. J Vasc Med Biol 2: 26–31Google Scholar
- 27.Hamet P, Tremblay J (1989) Abnormalities of second messenger systems in hypertension. In: Meyer P, Marche P (eds) Blood cells and arteries in hypertension and atherosclerosis. Raven, New York, pp 171–187Google Scholar