The natriuretic peptide (NP) family comprises three principal members which are released in response to hypervolaemic and hypertensive states. Atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) are all involved in the maintenance of electrolyte-fluid balance and vascular tone; as their name suggests, they promote natriuresis and diuresis resulting in loss of sodium and water thereby lowering blood volume and blood pressure. CNP was the third NP to be identified, first purified in 19901 some 10 years after the discovery of ANP2. CNP is the most widely expressed NP, with hotspots including the brain, chondrocytes and endothelial cells. CNP is thought to act locally, as a paracrine/autocrine regulator, since it is cleared rapidly from the circulation and present at very low concentrations in plasma3. It does not possess the potent diuretic actions that are observed with ANP and BNP3-5, but it is well established that exogenous CNP is a potent arterial- and veno- dilator of isolated mammalian blood vessels6-13 and infusion of CNP lowers blood pressure in several species, including humans14-17. Indeed, CNP has also been characterised as an endothelium-derived hyperpolarizing factor (EDHF)7. CNP also exerts direct cardiac effects where it acts as an inotropic and chronotropic agent18-20 and reduces aldosterone synthesis21. Chronic regulation of blood pressure by CNP also includes a central component through suppression of ACTH21, vasopressin22, and sympathetic outflow23. CNP exerts a number of physiological effects outside the cardiovascular system; perhaps its primary role being regulation of bone growth24-26, but it likely serves other functions such as neuronal development27, neuroprotection28, and reproduction29. CNP gene (Nppc) disruption has revealed the importance of CNP in terms of bone growth (endochondral ossification). Nppc KO mice exhibit dwarfism with the length of femurs, tibiae and vertebrae being 50 – 80 % of their wild-type littermates, in addition to striking narrowing of the growth plate25. Less than 50 % of CNP knockouts (KOs) are able to survive during postnatal development, although targeted expression of CNP in the growth plate chondrocytes improves their survival rate24.