Calcitonin gene-related peptide and hypertension.
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.
Deng
Pan-Yue
PY
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Xiang-Ya Road #90, Changsha, Hunan 410078, China.
Li
Yuan-Jian
YJ
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D016232:Endothelins / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D051381:Rats; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D050916:TRPV Cation Channels / Q000819:agonists; D014664:Vasodilation / Q000187:drug effects
D016232:Endothelins; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D015740:Calcitonin Gene-Related Peptide