MATURATION ALTERS CALCIUM DEPENDENT SENSITIVITYOFPRESSUREDEPENDENT CEREBROVASCULAR MYOGENIC TONE

Abstract

We tested the hypotheses that development alters sensitivity of pressure‐evoked myogenic constriction via increased sensitivity to calcium, and is more dependent on extracellular calcium in pups than in adults. We measured pressure‐evoked myogenic tone (20–80 mmHg) and changes in wall intracellular calcium concentration ([Ca 2+ ]i) in endothelium denuded, fura‐2 loaded middle cerebral arteries (MCA) from adult (6 month) and pup (P14) Sprague‐Dawley rats. Constriction and associated increases in active wall tension as a function of pressure were greater in pup compared to adult MCAs. At each pressure step wall [Ca 2+ ]i was also greater in pup than adult MCA. Nifedipine significantly attenuated pressure‐evoked constriction in MCA from adult, and eliminated all response to pressure in pups. To estimate the role of extracellular calcium in the myogenic response, we measured pressure‐evoked constriction at each pressure step over an extracellular calcium range from 0.1 μM to 1.8 mM. When active wall tension was normalized to wall [Ca 2+ ]i there was no significant difference in active wall tension over the applied range of extracellular calcium concentrations between adult and pup MCA. These data suggest that the myogenic response to pressure increments is more dependent on calcium influx during early development. In addition, during early development the increased sensitivity of pressure‐evoked myogenic response appears to be dependent on higher wall [Ca 2+ ]i as opposed to a greater sensitivity of myofilaments to changes in [Ca 2+ ]i Supported by NIH R01 #HL69078‐01 and NIH P01 #31226