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 art eries from most vascular beds, and this myogenic response has been sho wn to play an important role in the regulation of blood flow in the ki dney and other organs. The myogenic response in isolated perfused arte ries 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 arachidoni c acid potentiates, whereas inhibitors of cytochrome P-450 and protein kinase C attenuate, this response. Renal arteries produce 20-hydroxye icosatetraenoic acid (20-HETE) via the cytochrome P-450 pathway when i ncubated with arachidonic acid. 20-HETE is a potent constrictor of can ine and rat renal arterioles. It inhibits K+ channel activity, depolar izes renal vascular smooth muscle cells, and produces a sustained incr ease in intracellular calcium concentration. In this regard, the vasoc onstrictor response to 20-HETE mimics the myogenic activation of renal arteries after elevations in transmural pressure. These studies sugge st that the activation of phospholipase C and subsequent increases in the intracellular levels of diacylglycerol, 1,4,5 inositol triphosphat e, and cytochrome P-450 metabolites of arachidonic acid may participat e in the myogenic response of renal arteries and in the regulation of renal vascular tone.