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+)-ATPase (10 μM cyclopiazonic acid), IP3 receptor (100 μM 2-APB), Ca(2+)-activated Cl(-) channels (100 μM DIDS) or store-operated Ca(2+) entry channels (10 μM SKF96365). 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.
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+)-ATPase (10 μM cyclopiazonic acid), IP3 receptor (100 μM 2-APB), Ca(2+)-activated Cl(-) channels (100 μM DIDS) or store-operated Ca(2+) entry channels (10 μM SKF96365). 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.