Angiotensin II Decreases the Renal MRI Blood Oxygenation Level–Dependent Signal

Abstract

Abstract-Acute experimental reduction of renal blood flow decreases the renal blood oxygenation level-dependent (BOLD) MRI signal in animals. Angiotensin II also reduces renal blood flow, but the ability of BOLD MRI to dynamically detect this response has not yet been investigated in humans. Six healthy male volunteers underwent an individual dose-finding study to identify the intravenous doses of angiotensin II, norepinephrine, and sodium nitroprusside necessary to induce a 15-mm Hg peak mean arterial blood pressure change. MRI studies followed within 3 weeks, when angiotensin II (8.8Ϯ1.4 ng/kg), norepinephrine (52Ϯ12 ng/kg), and sodium nitroprusside (2.0Ϯ0.3 g/kg) were given twice in an unblocked, randomized sequence while imaging experiments were performed on a 1.5-T Siemens Sonata. A multiecho echo-planar imaging sequence was used to acquire T2* maps with a temporal resolution of 1 respiratory cycle. Averaged over a renal cortex dominated region of interest, angiotensin II caused a shortening of T2* between 6% and 10%. Sodium nitroprusside and norepinephrine, although of equal potency concerning blood pressure responses, did not alter the renal BOLD signal. The renal BOLD response to angiotensin II appeared with short onset latency (as early as 10 seconds after peripheral intravenous angiotensin II bolus administration) suggesting that this response is a consequence of altered perfusion rather than increased renal oxygen consumption. This effect is likely mediated by the kidneys. 3,4 A2 affects a variety of kidney functions potentially influencing long-term BP control, such as renal handling of sodium 5 and renal hemodynamics. 6 Clearance techniques may be applied in humans to study such effects but are time consuming. Alternative noninvasive techniques are warranted. It was demonstrated recently in animals that acute experimental reduction of renal perfusion pressure, with subsequent reduction of renal blood flow, diminishes the renal blood oxygenation level-dependent (BOLD) MRI signal. 7,8 BOLD MRI exploits the fact that the different magnetic susceptibilities of oxygenated and deoxygenated hemoglobin result in locally different effective transversal relaxation rates. Therefore, changes in tissue oxygenation can be detected by BOLD MRI via altered concentrations of deoxyhemoglobin. Because A2 reduces renal blood flow, 6,9 we hypothesized that A2 reduces the renal BOLD MRI signal, as well. Norepinephrine (NE) and sodium nitroprusside (SNP) are potent vasoactive substances with excellent dose-response characteristics. They may be administered in individually adjusted doses as to affect arterial BP and renal perfusion pressure at the same extend as does A2. Previous research indicated NE 10,11 and SNP 12,13 to have little or no impact on renal perfusion because of renal autoregulation. Thus, we hypothesized that NE and SNP also have no effect on the BOLD MRI signal and used these substances as control interventions. MethodsSix healthy male volunteers (mean age, 26; range, 22 to 29 years; body weight, 71.2; ra...

Blood oxygenation level-dependent MRI for assessment of renal oxygenation

“…17 Administration of angiotensin II to healthy male subjects examined by BOLD MRI (n=6) led to renal hypoxia. 36 In healthy subjects (n=9) studied 2 hours after administration of an angiotensin receptor antagonist, cortical but not medullary oxygenation increased. 37 In another group of healthy subjects (n=5), no change in oxygenation of the renal cortex or medulla was observed after chronic treatment with a direct renin inhibitor or after acute administration of an angiotensin-converting enzyme inhibitor.…”

Activation of the Renin-Angiotensin System and Chronic Hypoxia of the Kidney

“…Of note, hypoxia of the kidney by angiotensin II has also been demonstrated in humans. Schachinger et al studied the effects of vasoactive agents on kidney oxygenation in humans utilizing BOLD-MRI (46). Angiotensin II caused an immediate shortening of T2*, in contrast to other vasoactive agents which had no effect on the renal BOLD signal.…”

Noninvasive Evaluation of Kidney Hypoxia and Fibrosis Using Magnetic Resonance Imaging

“…In patients with diabetic nephropathy, the ADC values significantly correlated with eGFR in a manner identical to that of nondiabetic CKD ( Figure 2D). In contrast, there was no correlation between T2* values and eGFR, although several subjects showed lower T2* values than (8) Acute interstitial nephritis (8) Chronic glomerulonephritis (37) Acute glomerulonephritis (3) Chronic interstitial nephritis (7) Asymptomatic hematuria (4) The study participants were diagnosed with either CKD without diabetes, diabetic nephropathy, or AKI without diabetes. No significant differences were observed between the CKD without diabetes and diabetic nephropathy groups.…”

“…5 The second promising MRI technique, BOLD-MRI, noninvasively assesses tissue oxygen bioavailability by measuring relative changes in deoxyhemoglobin, an endogenous contrast agent. 6,7 BOLD-MRI, which was developed primarily for visualizing active regions in the brain, has been used ex-perimentally to demonstrate acute and transient changes in oxygenation levels in the renal cortex 8 and medulla. 9 -11 Additionally, the capability of BOLD-MRI to evaluate chronic, progressive, parenchymal hypoxia in renal allografts has been reported.…”