Kidneys in hypertensive rats show reduced response to nitric oxide synthase inhibition as evaluated by BOLD MRI

Abstract

Purpose: To examine whether the noninvasive technique of blood oxygenation level dependent magnetic resonance imaging (BOLD MRI) can detect changes in renal medullary oxygenation following administration of a nitric oxide (NO) synthase inhibitor, N G -nitro-L-arginine methyl ester (L-NAME). Hypertension is associated with endothelial dysfunction and is characterized by a lack of response to endothelial-dependent vasoactive substances, including nitric oxide synthase inhibitors. We hypothesized that the magnitude of the change would be reduced in the kidneys of hypertensive subjects relative to normal controls. Materials and Methods:To test this hypothesis, data were obtained in spontaneously hypertensive rats (SHR, n ϭ 6). Wistar-Kyoto rats (WKY, n ϭ 7) were used as normotensive controls. Results:As expected, WKY rats showed a significant response to L-NAME (R 2 * increasing from 23.6Ϯ1.5 Hz to 32.5Ϯ2.2 Hz, P Ͻ 0.05), while SHR exhibited a minimal change in medullary oxygenation (R 2 * measuring 31.9Ϯ2.8 Hz pre-and 35.5Ϯ2.2 Hz post-L-NAME). The baseline R 2 * in SHR is found to be comparable to post-L-NAME values in WKY rats, suggesting a basal deficiency of nitric oxide in SHR. Conclusion:Based on the differential effect of NO synthase inhibition on medullary oxygenation, BOLD MRI can distinguish hypertensive from normal kidney. Our results are consistent with previously reported observations using invasive methods.

Evaluation of the reproducibility of intrarenal R and ΔR measurements following administration of furosemide and during waterload

“…However, the lack of a significant and reliable response following the water diuresis must be taken into consideration for experiments designed to be used with the waterload paradigm. Direct stimulation/inhibition of the prostaglandin system may be a more robust paradigm, similar to our recent finding that nitric oxide inhibition has a reduced response in hypertensive kidneys (16). A recent report from Zuo et al (17) illustrated the spatial heterogeneity in response to waterload within an individual kidney.…”

Early Changes With Diabetes in Renal Medullary Hemodynamics as Evaluated by Fiberoptic Probes and BOLD Magnetic Resonance Imaging

“…It is also important to point out that the inner medulla on the map is relatively dark even though it has been shown previously based on microelectrode measurements that the tissue pO 2 may be the lowest in this region. 15,45 This has been a consistent finding to date, 20,21,23,26,27 and we do not yet know the exact cause. It might result from high fluid content in inner medulla.…”

“…Blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) has been shown to be very useful in monitoring intrarenal oxygenation. [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] A major advantage of the noninvasive BOLD MRI is the ability to perform similar measurement in humans.…”

Evaluation of Intra-Renal Oxygenation by BOLD MRI

“…Our recent data using BOLD MRI show that NO bioavailability is reduced in kidneys of hypertensive rats [47], and may be increased by suitable pharmacological interventions such as superoxide scavengers [48]. This was done by demonstrating that the baseline R 2 * values in the renal medulla of spontaneously hypertensive rat (SHR) were significantly higher than those in Wistar-Kyoto (WKY) strain (implying lower oxygenation) and that they do not respond to nitric oxide synthase (NOS) inhibition by L -NAME (fig.…”