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Modulation of synovial blood flow by the calcitonin gene‐related peptide (CGRP) receptor antagonist, CGRP (8–37)
Author(s) -
McMurdo Lorraine,
Lockhart J C,
Ferrell W R
Publication year - 1997
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 - 10.1038/sj.bjp.0701237
Subject(s) - calcitonin gene related peptide , calcitonin , endocrinology , medicine , blood flow , antagonist , receptor antagonist , receptor , neuropeptide
The effect of the calcitonin gene‐related peptide (CGRP) receptor antagonist, CGRP (8–37) on blood flow in the knee joint of the anaesthetized rat was investigated. Synovial blood flow in both exposed and intact, skin‐covered knees was measured by laser Doppler perfusion imaging. Topical application of CGRP (8–37) caused a dose‐dependent fall in synovial blood flow in the exposed knee joint of the rat. At low (1.5nmol) doses of CGRP (8–37) there was no significant effect on synovial blood flow. In rats treated with 7.5nmol CGRP (8–37) there was a fall in synovial blood flow (maximum effect at 10min: −28.8±4.6%; n =7), which returned to resting levels within 30min. The highest dose (15nmol) of antagonist used in this study caused a marked (maximum at 10min: −35.6±9.3%; n =8), and prolonged (up to 30min) fall in blood flow. Ten days after surgical denervation, CGRP (8–37) (15nmol, topical) had no significant effect on blood flow in the rat exposed knee joint (change in flux at 10min: −5.1±3.6%; n =4). This suggests that CGRP (8–37) acts selectively to antagonize the actions of a neurally derived product, probably CGRP, on the rat synovial vasculature. In skin‐covered knee joints, intra‐articular injection of CGRP (8–37) (15nmol; bolus) elicited a significant fall in synovial blood flow (maximum effect at 10min: −15.5±5.8%; n =6). CGRP (0.01, 0.1 or 1.0nmol; topical) caused a dose‐dependent increase in exposed knee joint blood flow, which was attenuated by co‐administration of 1.5nmol CGRP (8–37) . For example, 1nmol CGRP elicited a peak increase in flux at 10min of 94.7±31.8% ( n =8) and 28.8±8.9% ( n =7) in the absence and presence of CGRP (8–37) , respectively. The vasodilator responses induced by acetylcholine (ACh) (10nmol, topical; n =4–5) or sodium nitroprusside (SNP) (10nmol, topical; n =4–5) were unaltered in the presence of CGRP (8–37) (1.5nmol, topical). Thus, the CGRP receptor antagonist CGRP (8–37) elicits vasoconstriction in the rat synovium. This suggests that the endogenous, basal release of CGRP may play a physiological role in the regulation of blood flow in the rat knee joint.