Letter by Tsuda Regarding Article, “A Novel α-Calcitonin Gene-Related Peptide Analogue Protects Against End-Organ Damage in Experimental Hypertension, Cardiac Hypertrophy, and Heart Failure”
Authors: Kazushi Tsuda
Journal: Circulation (2018)

I read with great interest the article by Dr Aubdool and colleagues 1 dealing with the effects of a novel potent and long-lasting acetylated α-calcitonin gene-related peptide (α-CGRP) analogue on cardiovascular damages in 2 distinct murine models of hypertension and heart failure in vivo.The results of their study demonstrated that the angiotensin II-induced hypertension was attenuated by cotreatment of α-CGRP analogue.The α-CGRP analogue protected against vascular, renal, and cardiac dysfunction, characterized by reduced hypertrophy and biomarkers of fibrosis, remodeling, inflammation, and oxidative stress.In addition, the authors showed that the α-CGRP analogue reversed angiotensin II-induced hypertension and associated vascular and cardiac damage.The α-CGRP analogue was also effective in an abdominal aortic constriction model of murine cardiac hypertrophy and heart failure.The findings might support the hypothesis that CGRP could protect against adverse remodeling, inflammation, oxidative stress, apoptosis, and end-organ damage in cardiovascular disease.The authors proposed that the CGRP pathway would be a therapeutic target for the clinical treatment of cardiovascular disease.It is well recognized that enhanced activity of the sympathetic nervous system likely participates in the pathogenesis and development of hypertension. 2Several lines of evidence demonstrate that α-CGRP might inhibit the sympathetic nerve activity in both the central and peripheral nervous systems.Previously, we showed that α-CGRP inhibited the stimulation-evoked noradrenaline release from rat hypothalamus in a dose-dependent manner. 3It was also demonstrated that a dihydropyridine-sensitive Ca channel agonist Bay K8644 significantly reversed the inhibitory effect of α-CGRP on noradrenaline release. 3The finding suggests that α-CGRP might partially interact with the dihydropyridine-sensitive Ca channels and reduce the sympathetic nerve activity in the central nervous system.In addition, it was shown that inhibitory action of α-CGRP on noradrenaline release was significantly attenuated in spontaneously hypertensive rats compared with normotensive Wistar-Kyoto rats. 4 In the periphery, it was reported that α-CGRP reduced the contraction induced by the sympathetic nerve stimulation in rat vas deferens. 5In this context, it is strongly suggested that the sympatholytic action of α-CGRP would be related, at least in part, to the protection of hypertension and hypertension-induced end-organ damage.Because the authors described that increased renal noradrenaline content in the angiotensin II-induced hypertension was restored by the α-CGRP analogue, I would like to know whether the magnitudes of the α-CGRP analogue-dependent amelioration of blood pressure, cardiac hypertrophy, and heart failure might be associated with the changes of the sympathetic nerve activity in the study of Dr Aubdool and colleagues.Further studies should be performed to assess more thoroughly the interaction between CGRP and the sympathetic nervous system and its contribution to the protective effects against hypertension and cardiovascular damage.