title: Calcium and abnormal reactivity of vascular smooth muscle in hypertension.
abstract: It has been well documented that vascular smooth muscle (VSM) reactivity, as well as calcium sensitivity in response to neurotransmitters is increased in a number of blood vessels in established hypertension. Regulation of VSM reactivity involves the interaction of neurotransmitters and blood-borne hormones with specific receptors on target cell membranes. This results in phospholipase-C-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) and the generation of two second messengers: inositol 1,4,5 trisphosphate (IP3) and diacylglycerol (DAG) both of which act synergistically to produce muscle contraction. We will summarize recent findings in this review which suggest that in essentially hypertensive patients and spontaneously hypertensive rats (SHR), the activation of phospholipase C in response to hormones is increased. Further, we will discuss how increases in phospholipase C activation via GTP-binding proteins may explain the observed increases in Ca2+ influx through potential- and receptor-operated Ca2+ channels, increased activation of protein kinase-C and increased [Ca2+]i in hormone-stimulated blood platelets and VSM cells in the hypertensive state. In addition to these defects, a decrease in the plasma membrane Ca2+ pump and Ca2+-binding proteins has been demonstrated in hypertension. Thus, it appears that the defect in Ca2+ metabolism in the hypertensive vessels is multifocal. All these defects in Ca2+ metabolism together may lead to an increase in peripheral vascular resistance with a concomitant increase in blood pressure.
authors.affiliation: Department of Anatomy, College of Medicine, University of Iowa.
authors.forename: R V
authors.initials: RV
authors.lastname: Sharma
authors.forename: R C
authors.initials: RC
authors.lastname: Bhalla
mesh_terms: D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D003593:Cytoplasm / Q000032:analysis; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D011493:Protein Kinase C; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D002118:Calcium