Renin–angiotensin–endothelin–CGRP vascular pathway

The Renin–angiotensin–endothelin–CGRP vascular pathway is a complex physiological network comprising several distinct but interacting systems that maintain cardiovascular and hemodynamic stability. The Renin-Angiotensin System (RAS) produces Angiotensin II, a potent vasoconstrictor that acts via the AT1 receptor to increase blood pressure and promote fibrosis (StatPearls, 2023). The Endothelin system, primarily through Endothelin-1 acting on ET_A and ET_B receptors, serves as the most potent endogenous vasoconstrictor and is often upregulated in pulmonary hypertension (PubMed, 2021). Conversely, the Calcitonin Gene-Related Peptide (CGRP) is a powerful vasodilator released from perivascular nerves that plays a protective role in the cardiovascular system but is also a key mediator in the pathophysiology of migraines (Nature Reviews Neurology, 2018). Drugs targeting this pathway include ACE inhibitors and ARBs for hypertension, endothelin receptor antagonists for pulmonary arterial hypertension, and CGRP receptor antagonists for migraine prophylaxis. Therapeutic challenges include managing the balance between systemic blood pressure and local tissue perfusion, as well as avoiding side effects like hyperkalemia or angioedema associated with RAS inhibition.

Other names

Renin-angiotensin systemEndothelin systemCGRP signaling pathwayVascular regulatory networkNeuro-hormonal vascular pathway

Inhibition of vasoconstrictive enzymes (ACE, Renin), blockade of vasoconstrictive receptors (AT1, ET_A/ET_B), or blockade of vasodilatory neuropeptide receptors (CGRP receptor) to modulate vascular tone and blood pressure.