title: Nitric oxide regulation of ADP-ribosylation of G proteins in hypertension.
abstract: Nitric oxide stimulates endogenous ADP-ribosylation of cytosolic and membrane-bound proteins. Endogenous ADP-ribosyltransferases modify several intracellular proteins including the heterotrimeric GTP-binding proteins (G proteins). ADP-ribosylation of G proteins in vascular smooth muscle leads to increased activation of adenylate cyclase and decreased activation of phospholipase C leading to vasodilation. We hypothesize that in hypertension, chronically depressed endothelium-derived nitric oxide levels lead to decreased ADP-ribosylation of G proteins. This reduced ADP-ribosylation leads to vasoconstriction since activation of the G proteins by agonists is unopposed. Thus, disinhibition of G proteins, mediated by nitric oxide deficit, is responsible for the observed increased sensitivity to vasoconstrictor agonists in hypertension. This novel role for nitric oxide in hypertension will provide a new area of research for antihypertensive therapeutic intervention.
authors.affiliation: University of Michigan Medical School, Ann Arbor 48109-0622, USA.
authors.forename: N L
authors.initials: NL
authors.lastname: Kanagy
authors.forename: J R
authors.initials: JR
authors.lastname: Charpie
authors.forename: R C
authors.initials: RC
authors.lastname: Webb
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology / Q000503:physiopathology; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D008955:Models, Cardiovascular; D009131:Muscle, Smooth, Vascular / Q000502:physiology / Q000503:physiopathology*; D009569:Nitric Oxide / Q000502:physiology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism; D014664:Vasodilation
chemical_list: D000246:Adenosine Diphosphate Ribose; D009569:Nitric Oxide; D011065:Poly(ADP-ribose) Polymerases; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases