Cellular and ionic signal transduction mechanisms for the mechanical activation of renal arterial vascular smooth muscle.
Elevations in transmural pressure increase active vascular tone in arteries from most vascular beds, and this myogenic response has been shown to play an important role in the regulation of blood flow in the kidney and other organs. The myogenic response in isolated perfused arteries is associated with depolarization of vascular smooth muscle cells and a rise in intracellular calcium concentration, which is dependent on calcium influx through voltage-sensitive calcium channels. Recent studies have indicated that the myogenic response in renal arteries is associated with the activation of phospholipase C and that arachidonic acid potentiates, whereas inhibitors of cytochrome P-450 and protein kinase C attenuate, this response. Renal arteries produce 20-hydroxyeicosatetraenoic acid (20-HETE) via the cytochrome P-450 pathway when incubated with arachidonic acid. 20-HETE is a potent constrictor of canine and rat renal arterioles. It inhibits K+ channel activity, depolarizes renal vascular smooth muscle cells, and produces a sustained increase in intracellular calcium concentration. In this regard, the vasoconstrictor response to 20-HETE mimics the myogenic activation of renal arteries after elevations in transmural pressure. These studies suggest that the activation of phospholipase C and subsequent increases in the intracellular levels of diacylglycerol, 1,4,5 inositol triphosphate, and cytochrome P-450 metabolites of arachidonic acid may participate in the myogenic response of renal arteries and in the regulation of renal vascular tone.
Roman
R J
RJ
Harder
D R
DR
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001696:Biomechanical Phenomena; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D051381:Rats; D012077:Renal Artery / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D010738:Type C Phospholipases / Q000502:physiology
D006893:Hydroxyeicosatetraenoic Acids; D007473:Ion Channels; D016718:Arachidonic Acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D010738:Type C Phospholipases