Role of the angiotensin AT2 receptor in blood pressure regulation and therapeutic implications

Abstract

The angiotensin (ANG) Type 2 (AT2) receptor is one of two major ANG II receptors that have been identified, cloned, and sequenced. Most of the biologic actions of ANG II are thought to be mediated by the AT1 receptor, but evidence is beginning to emerge that the AT2 receptor has a significant role in the regulation of blood pressure. In the adult rat, the AT2 receptor is expressed, albeit in low concentrations in kidney, mesenteric blood vessels, and heart. Most of the evidence suggests that the AT2 receptor stimulates a vasodilator signaling cascade that includes bradykinin, nitric oxide, and guanosine cyclic 3',5'-monophosphate. At lease some of the beneficial actions of AT1 receptor blockade are mediated by the AT2 receptor through this pathway. Several recent studies suggest that AT2 receptors may mediate vasodilation and hypotension. The AT2 receptor represents a potential therapeutic target for agonist action and a candidate molecule in the pathophysiology of hypertension.

Rat Strain Effects of AT 1 Receptor Activation on D 1 Dopamine Receptors in Immortalized Renal Proximal Tubule Cells

“…[1][2][3][4][5][6][7][8] Dopamine promotes natriuresis, whereas angiotensin II decreases sodium excretion. [1][2][3][4][5][6][7][8] The major D 1 -like receptor subtype mediating the increase in sodium excretion is probably the D 1 receptor, whereas the major angiotensin II receptor mediating the decrease in renal sodium excretion is the AT 1 receptor. [1][2][3][4][5][6][7][8] In SHRs, renal proximal tubular D 1 receptor function is impaired.…”

“…The current studies were designed to test the hypothesis that activation of the AT 1 receptor can also regulate the D 1 receptor in RPT cells, and this regulation is aberrant in spontaneously hypertensive rats (SHRs Key Words: dopamine Ⅲ kidney Ⅲ receptors, angiotensin II Ⅲ rats, spontaneously hypertensive A ngiotensin II and dopamine are important regulators of sodium and water transport across the renal proximal tubule (RPT). [1][2][3][4][5][6][7][8] Angiotensin II receptor subtypes (AT 1 , AT 2 , and AT 4 ) are expressed in brush border and basolateral membranes of RPTs. [1][2][3][4][5] The activation of AT 1 receptors by low concentrations of angiotensin II (picomolar) causes an increase in sodium reabsorption in RPTs.…”

“…[1][2][3][4][5][6][7][8] Angiotensin II receptor subtypes (AT 1 , AT 2 , and AT 4 ) are expressed in brush border and basolateral membranes of RPTs. [1][2][3][4][5] The activation of AT 1 receptors by low concentrations of angiotensin II (picomolar) causes an increase in sodium reabsorption in RPTs. 1,3,6 All the dopamine receptor subtypes, D 1 -like (D 1 and D 5 ) and D 2 -like (D 2 , D 3 , and D 4 ) are also expressed in brush border and basolateral membranes of RPTs.…”

Can Angiotensin II Type 2 Receptors Have Deleterious Effects in Cardiovascular Disease?

“…AT 2 is believed to induce essentially opposite effects, including vasodilation and antigrowth and antihypertrophic effects, [1][2][3] and to play a significant role in blood pressure (BP) regulation. 4 The 2 major pharmacological inhibitors of the RAS, which are now important elements in the treatment of hypertension and cardiovascular disease, are ACE inhibitors and angiotensin receptor blockers (ARBs). These 2 classes of drugs have different effects on the RAS: suppression of Ang II production by ACE inhibitors reduces activation of both Ang II receptor subtypes, whereas ARBs preferentially block AT 1 and leave AT 2 unopposed.…”

Fetal development of regulatory mechanisms for body fluid homeostasis

“…More interestingly, the AT2 receptor has been shown to be reexpressed in the adult animal after cardiac and vascular injury or during wound healing, suggesting a role for this receptor in tissue remodeling, growth, or development. Recent and concordant data suggested (20) that overstimulation of AT2 receptors might be involved in cardiac and vascular hypertrophic processes, indicating that AT2 receptor may be involved in pathological processes in some diseases. In light of this, these chronic changes may also cause functional changes in body fluid regulation.…”