CALCIUM MOBILIZATION CONTRIBUTES TO PRESSURE-MEDIATED AFFERENT ARTERIOLAR VASOCONSTRICTION

Preglomerular responses to vasoactive agonists utilize calcium release d from intracellular stores and activation of calcium influx pathways to elicit vasoconstriction. The current study was performed to determi ne the role of calcium release from intracellular stores on the affere nt arteriolar response to increases in perfusion pressure. Experiments were performed, in vitro, using the blood perfused, juxtamedullary ne phron technique combined with videomicroscopy. The response of afferen t arterioles to 30 mm Hg increases in perfusion pressure was determine d before and after depletion of intracellular calcium pools with a 10- minute preincubation with 1 mu mol/L thapsigargin or 100 mu mol/L cycl opiazonic acid. Afferent arteriolar diameter averaged 20.2+/-1.0 mu m (n=19) at a control perfusion pressure of 100 mm Hg, Increasing perfus ion pressure to 130 and 160 mm Hg reduced afferent caliber by 10.7+/-1 .0% (P<.05 versus con) and by 24.7+/-1.6% (P<.05 versus diameter at 13 0 mm Hg); respectively. Thapsigargin significantly increased afferent diameter by 21+/-2% (n=6) at 100 mm Hg and prevented pressure-induced autoregulatory responses, Afferent diameter averaged 24.3+/-1.7, 24.5/-1.8 and 24.3+/-1.8 mu m at perfusion pressures of 100, 130 and 160 m m Hg; respectively. Cyclopiazonic acid treatment also inhibited autore gulatory behavior but did not alter resting vessel diameter. Afferent arteriolar diameter (n=6) averaged 21.4+/-1.9 mu m at 100 mm Hg and 20 .9+/-2.1 and 20.5+/-2.2 mu m at 130 and 160 mm Hg; respectively. Addit ional studies were performed to assess the role of phospholipase C act ivity in pressure-mediated autoregulatory behavior of afferent arterio les. Step increases in perfusion pressure decreased afferent diameter by 10.7+/-3.8 and 21.7+/-4.1%; respectively, Administration of the pho spholipase C inhibitor, U-73122, (5 mu moles/L) did not significantly alter baseline diameter but did attenuate the pressure-mediated vasoco nstrictor response. Increasing perfusion pressure to 130 and 160 mm Hg reduced afferent diameter by only 6.5+/-1.5 and 10.0+/-2.0%; respecti vely, These data demonstrate that interruption of calcium mobilization with thapsigargin, cyclopiazonic acid, or phospholipase C inhibition markedly attenuates pressure-mediated afferent arteriolar vasoconstric tion and suggests that autoregulatory adjustments in afferent arteriol ar diameter involve calcium release from inositoltrisphosphate(IP3)-se nsitive intracellular stores.