Calcitonin gene-related peptide and hypertension

Peptides. 2005 Sep;26(9):1676-85. doi: 10.1016/j.peptides.2005.02.002. Epub 2005 Mar 2.


Capsaicin-sensitive sensory nerves participate in the regulation of cardiovascular functions both in the normal state and the pathophysiology of hypertension through the actions of potent vasodilator neuropeptides, including calcitonin gene-related peptide (CGRP). CGRP, a very potent vasodilator, is the predominant neurotransmitter in capsaicin-sensitive sensory nerves, and plays an important role in the initiation, progression and maintenance of hypertension via: (1) the alterations in its synthesis and release and/or in vascular sensitivity response to it; (2) interactions with pro-hypertensive systems, including renin-angiotensin-aldosterone system, sympathetic nervous system and endothelin system; and (3) anti-hypertrophy and anti-proliferation of vascular smooth muscle cells. The decrease in CGRP synthesis and release contributes to the elevated blood pressure, as shown in the spontaneously hypertensive rats, alpha-CGRP knockout mice, Dahl-salt or phenol-induced hypertensive rats. In contrast, the increase in CGRP levels or the enhancement of vascular sensitivity response to CGRP plays a beneficial compensatory depressor role in the development of hypertension, as shown in deoxycorticosterone-salt, sub-total nephrectomy-salt, N(omega)-nitro-L-arginine methyl ester or two-kidney, one-clip models of hypertension in rats. We found that rutaecarpine causes a sustained depressor action by stimulation of CGRP synthesis and release via activation of vanilloid receptor subtype 1 (VR1) in hypertensive rats, which reveals the therapeutic implications of VR1 agonists for treatment of hypertension.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcitonin Gene-Related Peptide / pharmacology
  • Calcitonin Gene-Related Peptide / physiology*
  • Calcitonin Gene-Related Peptide / therapeutic use
  • Disease Models, Animal
  • Endothelins / metabolism
  • Humans
  • Hypertension / drug therapy
  • Hypertension / metabolism
  • Hypertension / physiopathology*
  • Mice
  • Muscle, Smooth, Vascular / drug effects
  • Rats
  • Renin-Angiotensin System / drug effects
  • Renin-Angiotensin System / physiology
  • Sympathetic Nervous System / drug effects
  • Sympathetic Nervous System / physiology
  • TRPV Cation Channels / agonists
  • Vasodilation / drug effects


  • Endothelins
  • TRPV Cation Channels
  • TRPV1 receptor
  • Calcitonin Gene-Related Peptide