Abstract
Dear Sir With great interest we read the article by Kruuse et al. (1), who reported the effects of a nitric oxide (NO) donor, glyceryl trinitrate (GTN) on calcitonin gene-related peptide (CGRP) release in man. In their study, GTN infusion had a significant vasodilatory effect on the intracranial and systemic circulation. However, this response was not accompanied by a measurable increase in jugular or cubital venous plasma CGRP levels.
In their discussion, the authors reviewed previous data which are in agreement with their findings. We would like to correct one of the references made by the authors and provide some additional evidence from human studies supporting the conclusions of the article.
The authors refer to a previous study by our group (2). In this study, a different NO donor, sodium nitroprusside (SNP) was infused into the brachial artery of migraine patients and control subjects and its effect on forearm blood flow (FBF) was assessed. However, in this study, no plasma CGRP levels were determined. Nonetheless, we believe the following data from human, in vivo studies are in agreement with the findings of Kruuse et al. (1): No change in cubital venous plasma CGRP levels 60 min after sublingual GTN administration (3), as referred to by Kruuse et al. No effect of CGRP8-37, a peptide CGRP receptor antagonist, on SNP-induced increase in FBF (4). No effect of the potent CGRP receptor antagonist telcagepant (MK-0974) on the increase in brachial artery diameter induced by sublingual nitroglycerin (5). No change in cubital venous plasma CGRP levels during local intra-brachial infusion of SNP (unpublished data from our group).
Thus, available data suggest that vasodilation induced by exogenous NO is not CGRP dependent in man; i.e. release of CGRP is not measurable in the cranial or systemic circulation and a CGRP-receptor antagonist does not inhibit the vasodilation. However, the reverse, i.e. the involvement of NO in CGRP-induced vasodilation, may well be the case as suggested by previous work from our group showing a partial inhibition of CGRP-induced forearm vasodilation by the NO synthase antagonist L-NMMA (6).