Calcium channel blockers, postural vasoconstriction and dependent oedema in essential hypertension

Treatment with calcium channel blocker (CCB)s, dihydropyridines and others, is frequently complicated by dependent oedema in the absence of sodium retention or cardiac failure, a bothersome side effect of unclear aetiology. The present paper reviews our own and other work dealing with the antagonism exerted by such drugs on postural vasoconstriction, a mechanism triggered by limb venous congestion during orthostasis and controlled through a local sympathetic axo-axonic reflex and increased myogenic tone in response to changes in transmural pressure. By stabilising capillary pressure, postural vasoconstriction counteracts fluid hyperfiltration consequent to gravitational stimuli, and consistent evidence shows attenuation of this response by L-type calcium channel blockers. Interference with the postural reflex control of skin blood flow may therefore contribute to dependent oedema, although cannot entirely explain its development. Attenuation of postural vasoconstriction may amplify the fluid hyperfiltration induced by CCBs through other mechanisms, such as imbalanced intracapillary pressure or enhanced vascular permeability, which are the main factors determining net fluid filtration into the interstitial compartment.