Effect of cyclooxygenase inhibition on renal blood flow autoregulation in SHR

Autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR) is well maintained in the spontaneously hypertensive rat (SHR). In old SHR, the RBF autoregulation is dependent upon prostaglandins as well as the sympathetic nervous system. The purpose of this study was to examine the role of nitric oxide (NO) in the autoregulation of RBF and GFR in aging SHR (70 weeks) as compared with young SHR (10 weeks) and age–matched Wistar–Kyoto (WKY) rats using NO synthase (NOS) inhibition that has a minimal effect on the RBF. The autoregulation of RBF was examined using an adjustable aortic clamp above the renal arteries and an ultrasound Doppler flow probe on the left renal artery. The lower pressure limit of RBF autoregulation was examined before and after infusion of the NOS inhibitor N^G–monometyl–L–arginine (L–NMMA; 500 μg·kg^–1·min^–1). Separate groups were given a coinfusion of L–NMMA and L–arginine (5 mg·kg^–1·min^–1) or Ringer solution. The autoregulation of the GFR was studied in continuously infused animals using the ¹²⁵I–iothalamate clearance. Measurements of the GFR were done at control blood pressure, at a renal arterial pressure 10 mmHg above the lower pressure limit of RBF autoregulation and at a renal arterial pressure of about 60–65 mmHg. In both SHR and WKY rats, infusion of L–NMMA increased the mean arterial blood pressure, and the RBF decreased in young SHR, while the RBF was unchanged in the WKY groups and aged SHR. The autoregulation of RBF was maintained in all animals. The GFR was unchanged in all groups after infusion of L–NMMA, and the autoregulation of GFR was well maintained in all groups except in the 70–week–old SHR. In these animals, the fractional compensation of GFR decreased from 0.95 to ∼ 0 after infusion of L–NMMA, indicating that autoregulation of the GFR was lost during NOS inhibition. Coinfusion of L–NMMA and L–arginine normalized the GFR autoregulation in this group. The results indicate that in hypertensive rats with renal hypertensive damage, the GFR autoregulation is strongly NO dependent, as doses of L–NMMA that do not interfere with the RBF have an effect on the GFR autoregulation. As the GFR was unchanged during L–NMMA infusion, these observations suggest that postglomerular contraction during NOS inhibition may be involved in the regulation of GFR in 70–week–old SHR.

Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 72%

Section: Discussionmentioning

confidence: 92%

See 1 more Smart Citation

Role of Nitric Oxide in the Autoregulation of Renal Blood Flow and Glomerular Filtration Rate in Aging Spontaneously Hypertensive Rats

Kvam

Ofstad

Iversen³

2000

“…The reduced numbers of V 1a receptors in old compared to young SHR described in the present paper are entirely in line with the hemodynamic findings. The old animals of both strains showed a similar vasoconstrictive response that was reduced compared to their respective strain at young age and this fact is best explained by the increased diameter of renal resistance vessels and hence decreased vasoconstrictive response in older animals [20].…”

Section: Discussionmentioning

confidence: 82%

Renal Hemodynamics in Young and Old Spontaneously Hypertensive Rats during Intrarenal Infusion of Arginine Vasopressin

Christiansen

Roald

Gjerstad

et al. 2001

Background/Aims: To gain insight into the effect of arginine vasopressin (AVP) on renal hemodynamics in hypertensive rats, we investigated the vasoconstrictive response to AVP on total renal blood flow (RBF) and total and zonal glomerular filtration rate (GFR) in young and old spontaneously hypertensive rats (SHR). A hypothesis of increased AVP sensitivity in the juxtamedullary cortex of SHR was tested. Methods: Total RBF and total and zonal GFR were studied in 10- and 40-week-old SHR and normotensive Wistar-Kyoto rats (WKY). RBF was recorded by a flowmeter before infusion of AVP and immediately after injection of a bolus dose of 10 ng AVP. Whole kidney GFR and its intracortical distribution was measured by the tubular uptake of ¹²⁵I- and ¹³¹I-labelled aprotinin before and during a continuous infusion of AVP 5 ng/min. Ligand binding measurements of preglomerular V_1a receptors were performed in young and old rats. Results: RBF decreased by 43 ± 3% in 10-week SHR (9.2 ± 0.5 vs. 5.2 ± 0.3 ml·min^–1·g^–1), significantly more than 10-week WKY where RBF decreased by 35 ± 3% (9.6 ± 0.7 vs. 6.5 ± 0.5 ml·min^–1·g^–1) (p < 0.05). The effect of AVP on RBF was attenuated in 40-week-old rats where the decline in RBF was 29 ± 5% in SHR and 23 ± 4% in WKY (p > 0.05). GFR decreased by 6 ± 3% (1.03 ± 0.04 vs. 0.96 ± 0.04 ml·min^–1·g^–1, p < 0.05) in 10-week SHR and was unchanged in 10-week WKY (1.10 ± 0.07 vs. 1.08 ± 0.04 ml·min^–1·g^–1, p > 0.10). GFR decreased by 11 ± 10% in 40-week SHR and by 4 ± 4% in 40-week WKY (p > 0.05). AVP infusion significantly increased filtration fraction in all groups except 40-week SHR, indicating that AVP has the strongest vasoconstrictive effect on postglomerular vessels. The intrarenal distribution of GFR was unchanged in the normotensive and hypertensive groups. V_1a receptor density was upregulated in young SHR compared to young WKY (p < 0.05), but downregulated in old compared to young SHR (p = 0.05). Conclusion: The results indicate that AVP sensitivity is not increased in the juxtamedullary cortex in SHR and the reduced vasoconstrictive effect in old SHR is due to a reduced density of V_1a receptors.

“…The mechanisms behind this phenomenon can only be revealed by micropuncture technique, but a decrease in preglomerular resistance due to blood pressure reduction might con tribute to maintain GFR. This GFR would be more likely to play a role in SHR in which preglomerular vascular resist ance is increased [34].…”

Section: Gfr Autoregulation In Mesangiolysismentioning

confidence: 99%

Autoregulation of Total and Zonal Glomerular Filtration Rate in Spontaneously Hypertensive Rats with Mesangiolysis

Wang

Aukland²,

Bostad³

et al. 1997

In this study we tested the hypothesis that mesangial cells participate in autoregulation of the glomerular filtration rate (GFR) in normotensive and hypertensive rats. Mesangial cell lesions were induced by intravenous administration of antithymocyte (anti-Thy 1.1) antibodies in spontaneously hypertensive rats (SHR) and in Wistar-Kyoto rats (WKY). Normal murine serum was injected in control rats. Hemodynamic measurements were performed 24 h after the infusion of the anti-Thy 1.1 antibodies. Renal blood flow (RBF) was measured by a transit time flowmeter (Transonic) and the GFR was measured as the uptake of ¹²⁵ iodine-labeled aprotinin (¹²⁵I-Ap) by proximal tubular cells at the control renal arterial pressure and ¹³¹I-Ap at a pressure reduction close to the lower pressure limit of RBF autoregulation. RBF was unaltered and the autoregulatory capability was maintained in SHR and WKY after mesangial cell lesions. Mesangiolysis significantly reduced the total GFR in normotensive, but not in hypertensive animals. The fractional compensation of the GFR was attenuated in the outer cortical layer (p < 0.05) in normotensive WKY In SHRs the fractional compensation of the GFR was impaired in all cortical layers after mesangiolysis, slightly more in the outer than in the inner cortex. We conclude that mesangial cells may contribute to the autoregulation of GFR in hypertensive rats, but to a lesser extent in normotensive rats.