Regulation by angiotensin II of its receptors in resistance blood vessels

Abstract

The sensitivity of blood vessels to the vasoconstrictor effects of the hormone angiotensin II appears to be modulated by the activity of the renin–angiotensin system. Elevation of circulating angiotensin II levels by sodium depletion or renal artery stenosis is associated with a diminished pressor response to infused angiotensin II (refs 1–3). Conversely, the vasoconstrictor response to the hormone is enhanced when endogenous angiotensin II levels are reduced by sodium loading1,4 or nephrectomy5. The mechanisms of these varying effects are not known, but physiological and pharmacological experiments suggest involvement of the vascular smooth muscle receptor for angiotensin II (refs 5–8). Modification of the interaction between angiotensin II and its vascular receptor, resulting in altered responsiveness to the hormone, could occur either via ‘prior occupancy’ of receptors by elevated levels of endogenous angiotensin II resulting in fewer free receptors available to respond to circulating angiotensin II (ref. 5), or, elevated levels of angiotensin II could result in a decrease in receptor affinity for the hormone7 or a decrease in total receptor number in the vascular smooth muscle cell8. We now report the first direct evidence, by radioligand binding assay, that angiotensin II regulates the number of its own receptors in resistance vasculature.