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GENERATION OF MYOGENIC TONE REQUIRES RELEASE OF CALCIUM IN RAT CEREBRAL ARTERIES
Author(s) -
Charles Shelton,
Zhang Lubo,
Longo Lawrence D,
Pearce William J,
Buchholz John N
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1386-a
Subject(s) - cyclopiazonic acid , calcium , extracellular , egta , serca , chemistry , cerebral arteries , calcium in biology , medicine , endocrinology , anatomy , voltage dependent calcium channel , atpase , biochemistry , enzyme
Myogenic response of cerebral arteries is defined as a change in blood vessel diameter in response to fluctuations in systemic blood pressure and participates in the modulation of cerebral blood flow. Our previous work has demonstrated that the pressure‐evoked constrictory response in the middle cerebral artery (MCA) is dependent on extracellular calcium influx through voltage‐operated calcium channels and possibly on the release of calcium from intracellular stores. In this study we measured pressure‐evoked changes in diameter and wall intracellular calcium ([Ca 2+ ]i) in isolated, endothelial denuded, Fura‐2 loaded segments of MCA (150 μm max diameter) from 6 month‐old male Sprague‐Dawley rats. Changes in diameter and [Ca 2+ ]i with increasing pressure steps (20, 40, 60, 80 mmHg) were measured in HEPES buffer (1.8 mM extracellular calcium) in the absence and presence of the sarcoplasmic reticulum calcium ATPase (SERCA) antagonist, Cyclopiazonic Acid (CPA, 10 μM), and after removal of extracellular calcium (0 Ca 2+ 3mM EGTA). In the absence of CPA, increased pressure produced significant development of myogenic tone (25%) with corresponding increases in [Ca 2+ ]i. When SERCA function was blocked by CPA, myogenic tone was significantly depressed from 54% to 90% over the pressure range with a corresponding significant decline in [Ca 2+ ]i. These data strongly suggest that release of calcium from SER is necessary for the development of pressure‐evoked myogenic tone in the rat cerebrovasculature. Supported by NIH R01 #HL69078‐01 and NIH P01 # 31226