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Properties of submucosal venules in the rat distal colon
Author(s) -
Mitsui Retsu,
Miyamoto Shun,
Takano Hiromichi,
Hashitani Hikaru
Publication year - 2013
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12347
Subject(s) - guanethidine , calcitonin gene related peptide , chemistry , phentolamine , endocrinology , medicine , stimulation , anatomy , neuropeptide , receptor
Background and Purpose Venules within the gut wall may have intrinsic mechanisms for maintaining the circulation even upon the intestinal wall distension. We aimed to explore spontaneous and nerve‐mediated contractile activity of colonic venules. Experimental Approach Changes in the diameter of submucosal venules of the rat distal colon were measured using video microscopy. The innervation of the microvasculature was investigated using fluorescence immunohistochemistry. Key Results Submucosal venules exhibited spontaneous constrictions that were abolished by blockers of L ‐type Ca 2+ channels (1 μM nicardipine), Ca 2+ ‐ATP ase (10 μM cyclopiazonic acid), IP 3 receptor (100 μM 2‐ APB ), Ca 2+ ‐activated Cl − channels (100 μM DIDS ) or store‐operated Ca 2+ entry channels (10 μM SKF 96365). Transmural nerve stimulation ( TNS at 10 Hz) induced a phasic venular constriction that was blocked by phentolamine (1 μM, α‐adrenoceptor antagonist) or sympathetic nerve depletion using guanethidine (10 μM). Stimulation of primary afferent nerves with TNS (at 20 Hz) or capsaicin (100 nM) evoked a sustained venular dilatation that was attenuated by calcitonin gene‐related peptide ( CGRP ) 8‐37 (2 μM), a CGRP receptor antagonist. Immunohistochemistry revealed sympathetic and primary afferent nerves running along submucosal venules. Conclusions and Implications Submucosal venules of the rat distal colon exhibit spontaneous constrictions that appear to primarily rely on Ca 2+ release from sarcoplasmic reticulum and subsequent opening of Ca 2+ ‐activated Cl – channels that trigger Ca 2+ influx through L ‐type Ca 2+ channels. Venular contractility is modulated by sympathetic as well as CGRP ‐containing primary afferent nerves, suggesting that submucosal venules may play an active role in regulating the microcirculation of the digestive tract.