The antihypertensive effect of calcitonin gene-related peptide in rats with norepinephrine- and angiotensin ll-induced hypertension

Fujioka, Shoji; Sasakawa, Osamu; Kishimoto, Hiroshi; Tsumura, Kei; Morii, Hirotoshi

doi:10.1097/00004872-199102000-00013

Cited by 19 publications

(14 citation statements)

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“…Indeed, the acute administration of exogenous αCGRP is known to decrease BP in the spontaneously hypertensive rat 22 also, over 6 days in the AngII-hypertensive rat. 23 However, an early study of AngII-induced hypertension in the rat did not show an upregulation of DRG CGRP expression. 24 Plasma CGRP levels were raised in hypertensive WT and αCGRPKO mice in the present study.…”

Section: Discussionmentioning

confidence: 96%

An Ongoing Role of α-Calcitonin Gene–Related Peptide as Part of a Protective Network Against Hypertension, Vascular Hypertrophy, and Oxidative Stress

et al. 2014

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1056α -Calcitonin gene-related peptide (αCGRP) is a potent vasodilator 1 and a hypotensive peptide. It is primarily localized to the sensory nervous system, with a perivascular innervation and considered to be the major cardiovascular form, as compared with the structurally similar βCGRP. CGRP acts via a G-protein-coupled receptor (calcitonin-like receptor) when dimerized with a single transmembrane-spanning receptor activity-modifying protein RAMP1 2 signaling via cAMP and other pathways. 3,4 CGRP does not play a primary role in the regulation of basal blood pressure (BP) in normal individuals 5,6 but is suggested to have protective properties, in cardiovascular disease, 7,8 including attenuation of vascular smooth muscle proliferation, 9 hyperplasia, 10,11 and stimulation of endothelial cell proliferation 12 and endothelial progenitor cells. 13 Evidence indicates the importance of CGRP in aggressive models of rodent hypertension that are centered on the kidney. 14,15 By comparison, there is little evidence of detailed analysis involving the ongoing influence of endogenous CGRP on hypertensive mechanisms and vascular remodeling, especially with regard to NO and oxidative stress pathways.Sensory nerve-derived CGRP release is stimulated by mechanisms that include angiotensin II (AngII) and sympathetic nerve reflexes, 3,4 baroreflex sensitivity, 16 and sensory nerve activators. 17,18 We have investigated the AngII hypertension model in wild-type (WT) and αCGRP knockout (αCGRPKO) mice that have similar resting BP. We hypothesized that αCGRP is protective against the onset and development of hypertension, and the aim was to identify mechanisms by which αCGRP is protective in this model. The novel findings show 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...

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Section: Discussionmentioning

confidence: 96%

An Ongoing Role of α-Calcitonin Gene–Related Peptide as Part of a Protective Network Against Hypertension, Vascular Hypertrophy, and Oxidative Stress

et al. 2014

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“…27 In contrast, CGRP infusion for 6 days had beneficial effects in hypertensive rats. 3 To build on this and elucidate the mechanisms, we show that the αAnalogue protects against AngII-induced increase in blood pressure for 2 weeks. We tested for potential desensitization by the daily administration of the αAnalogue in naive mice and found a reproducible hypotensive effect, with no signs of downregulation of the CGRP pathway in the vasculature.…”

Section: Discussionmentioning

confidence: 99%

“…Several CGRP receptor antagonists and antibodies developed as migraine therapies have minimal effect on blood pressure in healthy individuals. 1,2 Evidence that CGRP plays a role in cardiovascular protection arises from acute studies where CGRP has been administered in rodent models of hypertension, 3,4 using spontaneously hypertensive rats 5,6 and α-CGRP–specific knockout (KO) mice. 7 The beneficial effects of the native CGRP peptide have also been observed when administered for up to 24 hours to patients with congestive heart failure with no evidence of tolerance.…”

mentioning

confidence: 99%

A Novel α-Calcitonin Gene-Related Peptide Analogue Protects Against End-Organ Damage in Experimental Hypertension, Cardiac Hypertrophy, and Heart Failure

et al. 2017

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“…In one study where baseline blood pressure was not affected in CGRP KO mice, angiotensin administration for up to 28 days led to enhanced hypertension, alongside aortic hypertrophy and decreased endothelial nitric oxide synthase expression ( Smillie et al, 2014 ). In the rat angiotensin-induced hypertension model, the co-administration of subdepressor doses of exogenous CGRP for 6 days significantly reduced blood pressure ( Fujioka et al, 1991 ). However, in a 10-day study, angiotensin increased CGRP receptor expression but not endogenous CGRP levels ( Li and Wang, 2005 ).…”

Section: Cgrp In Cardiovascular Diseasementioning

confidence: 99%

The Role of Calcitonin Gene Related Peptide (CGRP) in Neurogenic Vasodilation and Its Cardioprotective Effects

2018

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Calcitonin gene-related peptide (CGRP) is a highly potent vasoactive peptide released from sensory nerves, which is now proposed to have protective effects in several cardiovascular diseases. The major α-form is produced from alternate splicing and processing of the calcitonin gene. The CGRP receptor is a complex composed of calcitonin like receptor (CLR) and a single transmembrane protein, RAMP1. CGRP is a potent vasodilator and proposed to have protective effects in several cardiovascular diseases. CGRP has a proven role in migraine and selective antagonists and antibodies are now reaching the clinic for treatment of migraine. These clinical trials with antagonists and antibodies indicate that CGRP does not play an obvious role in the physiological control of human blood pressure. This review discusses the vasodilator and hypotensive effects of CGRP and the role of CGRP in mediating cardioprotective effects in various cardiovascular models and disorders. In models of hypertension, CGRP protects against the onset and progression of hypertensive states by potentially counteracting against the pro-hypertensive systems such as the renin-angiotensin-aldosterone system (RAAS) and the sympathetic system. With regards to its cardioprotective effects in conditions such as heart failure and ischaemia, CGRP-containing nerves innervate throughout cardiac tissue and the vasculature, where evidence shows this peptide alleviates various aspects of their pathophysiology, including cardiac hypertrophy, reperfusion injury, cardiac inflammation, and apoptosis. Hence, CGRP has been suggested as a cardioprotective, endogenous mediator released under stress to help preserve cardiovascular function. With the recent developments of various CGRP-targeted pharmacotherapies, in the form of CGRP antibodies/antagonists as well as a CGRP analog, this review provides a summary and a discussion of the most recent basic science and clinical findings, initiating a discussion on the future of CGRP as a novel target in various cardiovascular diseases.

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The antihypertensive effect of calcitonin gene-related peptide in rats with norepinephrine- and angiotensin ll-induced hypertension

Cited by 19 publications

References 0 publications

An Ongoing Role of α-Calcitonin Gene–Related Peptide as Part of a Protective Network Against Hypertension, Vascular Hypertrophy, and Oxidative Stress

An Ongoing Role of α-Calcitonin Gene–Related Peptide as Part of a Protective Network Against Hypertension, Vascular Hypertrophy, and Oxidative Stress

A Novel α-Calcitonin Gene-Related Peptide Analogue Protects Against End-Organ Damage in Experimental Hypertension, Cardiac Hypertrophy, and Heart Failure

The Role of Calcitonin Gene Related Peptide (CGRP) in Neurogenic Vasodilation and Its Cardioprotective Effects

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