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 vasocontrictor response to the hormone is enhanced when endogenous angiotensin II levels are reduced by sodium loading or nephrectomy. The mechanisms of these varying effects are not known, but physiological and pharmacological experiments suggest involvement of the vascular smooth 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 hormone or a decrease in total receptor number in the vascular smooth muscle cell. We now report the first direct evidence, by radioligand binding assay, that angiotensin II regulates the number of its own receptors in resistance vasculature.

Altered sodium perception in essential hypertensive patients following rapid volume expansion

“…Changes in ambient Ang II concentrations affect the response of the vasculature by influencing the density of Ang II receptors. 8 We found that both saline and dextran were effective in suppressing PRA. Thus, increasing intravascular volume per se with saline or dextran produced signals (either intra-renal or extra-renal) which influenced renin-angiotensin system activity and altered responsiveness of these target tissues to Ang II.…”

Renin-angiotensin-aldosterone system in pregnancy-induced hypertension

“…9 Previously, studies have suggested that the ANG II receptor on platelet is regulated by ANG II in parallel with the receptor in the vasculature. 8 It is known that vascular smooth muscle ANG II receptor numbers change inversely with circulating ANG II concentrations. In consequence, a reduced biosynthetic ECA activity (present results), and thus a reduced plasma ANG II, may cause a feedback 'upregulation' of ANG II receptor number, as found in women with PIH.…”

“…7 At the same time vascular ANG II sensitivity is greatly reduced, as early as 14 weeks of gestation. 8 In women in whom PIH developed, there is a reduction in ANG II sensitivity early in pregnancy, but this reduction is lost after 22 weeks of gestation and predates the development of PIH. 3 At the same time vascular sensitivity is greatly increased, associated with increased ANG II binding in platelets 9 which have been found to mirror changes in the vascular ANG II receptor.…”

Angiotensin converting enzyme inhibition does not affect the response to exogenous angiotensin II in the human forearm.

“…This has been demonstrated in the vasculature [1], renal glomeruli [6] and hepatocytes [7]. Angiotensin II, however, positively modulates the expression of the receptor gene in the adrenal gland [8,9].…”

“…Animal studies have shown that the sensitivity of blood vessels to the vasoconstrictor effects of angiotensin II appears to be modulated by the activity of the renin-angiotensin system with the vasoconstrictor response being enhanced when endogenous angiotensin II levels are reduced by angiotensin converting enzyme inhibition [1], sodium loading [2] or nephrectomy [3]. Conversely, elevation of circulating angiotensin II levels by angiotensin II receptor antagonists [4], sodium depletion [2] or renal artery stenosis [5] is associated with a diminished pressor response to infused angiotensin II.…”