Angiotensin II and neurohumoral control of the renal medullary circulation

Abstract

1. Angiotensin (Ang) II has multiple actions in the renal medullary circulation. It can induce vasodilatation and blunt the response of medullary blood flow (MBF) to renal nerve activation through AT(1) receptor-mediated release of nitric oxide (NO) and/or vasodilator prostaglandins. These actions require high intravascular and/or intratubular AngII concentrations, so are not apparent under physiological conditions. 2. Nevertheless, these mechanisms blunt the responsiveness of MBF to AT(1) receptor-mediated vasoconstriction. When these protective mechanisms fail, as when oxidative stress reduces NO bioavailability in the medullary circulation, AngII reduces MBF. If sustained, reduced MBF leads to the development of hypertension. 3. Chronic activation of the renin-angiotensin system (RAS) induces oxidative stress in the kidney. Therefore, MBF may be reduced in models of hypertension associated with RAS activation both because AngII levels per se are increased and because of increased responsiveness of MBF to AngII-induced vasoconstriction. 4. Endogenous AngII enhances the responsiveness of MBF to renal nerve stimulation, whereas NO blunts it. Chronic RAS activation and/or oxidative stress should therefore be expected to enhance MBF responses to renal nerve stimulation. Consistent with this, reductions in MBF induced by renal nerve stimulation are enhanced in rabbits with AngII-induced hypertension, renovascular hypertension or after 9 weeks of fat feeding. 5. We conclude that the ability of endogenous AngII to reduce MBF and enhance the response of MBF to activation of the renal nerves could contribute to the development of hypertension under conditions of RAS activation, especially if accompanied by increased renal sympathetic nerve activity.

Moderate Intrarenal Vasoconstriction after High Pressor Doses of Norepinephrine in the Rat: Comparison with Effects of Angiotensin II

“…Remarkably, infusions of subpressor or slight pressor doses of Ang II decreased total renal or cortical blood flow while medullary perfusion usually increased or remained stable [10] . Using laserDoppler technique identical with that of the present study, we reported an increase [11] or no change [5] in MBF in anesthetized Wistar rats given Ang II at a rate which increased MAP by 2-3%.…”

“…Briefly, the vascular segments which control blood supply to the renal medulla are provided with AT 1 receptors which mediate Ang II-dependent vasoconstriction, however the circulating peptide stimulates a local release and action of vasodilator agents, mostly PGE 2 and NO, which effectively buffer or even overcompensate direct vasoconstriction [5,10] . The present results indicate that on application of Ang II at high pressor doses, the balance of direct vasoconstriction and secondary indirect vasodilation is shifted toward the former.…”

Blood Flow, Oxygenation, and Oxidative Stress in the Post-stenotic Kidney

“…Firstly, neurally-mediated renin release is blunted and secondly, neurally mediated vasoconstriction in the medullary circulation appears to be enhanced. These effects appear to be mediated predominantly by activation of the reninangiotensin system, since they are recapitulated in hypertension induced by chronic infusion of angiotensin II [ 74 ]. Angiotensin II is also likely a major driver of fi brosis during the evolution of RVD, at least partly through stimulation of the fi brogenic cytokine transforming growth factor-β (TGF-β) (Fig.…”

“…In the normal kidney, AT 1 -receptor activation by endogenous angiotensin II mediates cortical vasoconstriction, yet has little impact on the medullary circulation [ 74 ]. Activation of AT 2 -receptors by endogenous angiotensin II has little impact on cortical or medullary perfusion in the normal rat kidney [ 74 ].…”

Comparative Effect of a Renin Inhibitor and a Thiazide Diuretic on Renal Tissue Oxygenation in Hypertensive Patients

“…Angiotensin II has also a major impact on medullary blood flow and this may play an important role in the pathogenesis of hypertension. Indeed, a sustained angiotensin II-mediated reduction of medullary blood flow and the oxidative stress induced by an activation of the RAS have been associated with medullary ischemia and the development of salt-sensitive hypertension in animals [7][8][9]. Thus, the ability to measure renal tissue oxygenation and the impact of drugs affecting the RAS or renal sodium transport may be of interest to explore the pathogenesis of hypertension.…”