title: An ongoing role of α-calcitonin gene-related peptide as part of a protective network against hypertension, vascular hypertrophy, and oxidative stress.
abstract: α-Calcitonin gene-related peptide (αCGRP) is a vasodilator, but there is limited knowledge of its long-term cardiovascular protective influence. We hypothesized that αCGRP protects against the onset and development of angiotensin II-induced hypertension and have identified protective mechanisms at the vascular level. Wild-type and αCGRP knockout mice that have similar baseline blood pressure were investigated in the angiotensin II hypertension model for 14 and 28 days. αCGRP knockout mice exhibited enhanced hypertension and aortic hypertrophy. αCGRP gene expression was increased in dorsal root ganglia and at the conduit and resistance vessel level of wild-type mice at both time points. βCGRP gene expression was also observed and shown to be linked to plasma levels of CGRP. Mesenteric artery contractile and relaxant responses in vitro and endothelial NO synthase expression were similar in all groups. The aorta exhibited vascular hypertrophy, increased collagen formation, and oxidant stress markers in response to angiotensin II, with highest effects observed in αCGRP knockout mice. Gene and protein expression of endothelial NO synthase was lacking in the aortae after angiotensin II treatment, especially in αCGRP knockout mice. These results demonstrate the ongoing upregulation of αCGRP at the levels of both conduit and resistance vessels in vascular tissue in a model of hypertension and the direct association of this with protection against aortic vascular hypertrophy and fibrosis. This upregulation is maintained at a time when expression of aortic endothelial NO synthase and antioxidant defense genes have subsided, in keeping with the concept that the protective influence of αCGRP in hypertension may have been previously underestimated.
authors: Cardiovascular Division, King's College London, Franklin-Wilkins Building, London, SE1 9NH, United Kingdom. sue.brain@kcl.ac.uk.
authors: Sarah-Jane
authors: SJ
authors: Smillie
authors: Ross
authors: R
authors: King
authors: Xenia
authors: X
authors: Kodji
authors: Emilie
authors: E
authors: Outzen
authors: Gabor
authors: G
authors: Pozsgai
authors: Elizabeth
authors: E
authors: Fernandes
authors: Nichola
authors: N
authors: Marshall
authors: Patricia
authors: P
authors: de Winter
authors: Richard J
authors: RJ
authors: Heads
authors: Cecile
authors: C
authors: Dessapt-Baradez
authors: Luigi
authors: L
authors: Gnudi
authors: Anette
authors: A
authors: Sams
authors: Ajay M
authors: AM
authors: Shah
authors: Richard C
authors: RC
authors: Siow
authors: Susan D
authors: SD
authors: Brain
mesh_terms: D000804:Angiotensin II / Q000009:adverse effects / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D016232:Endothelins / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control*; D006984:Hypertrophy / Q000503:physiopathology / Q000517:prevention & control; D008643:Mesentery / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D016232:Endothelins; D000804:Angiotensin II; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; D015740:Calcitonin Gene-Related Peptide
keywords: angiotensin II; calcitonin gene-related peptide; hypertension; hypertrophy; mice; nitric oxide; oxidative stress