Effect of prostaglandin synthetase inhibitors on renal blood flow in the rat

Finn, WF; Arendshorst, WJ

doi:10.1152/ajplegacy.1976.231.5.1541

Cited by 56 publications

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“…The failure of cyclooxygenase inhibitors to increase RVR in our experiments (Table I, A) argues against a high level of PG activity in the rat kidney perfused at 40 mm Hg. These observations agree with those of other investigators (9,29), who report that cyclooxygenase inhibition has no effect on RVR in the rat at normal or moderately reduced RPP. Nevertheless, the possibility that PG are elevated in the ischemic rat kidney and that mannitol acts, not by stimulating production, but by overcoming vascular resistance to these hormones, can only be ruled out by direct measurement of PGI2 production.…”

Section: Discussionsupporting

confidence: 93%

Prostaglandins mediate the vasodilatory effect of mannitol in the hypoperfused rat kidney.

Johnston¹,

Bernard²,

Perrin³

et al. 1981

J. Clin. Invest.

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A B S T R A C T We have previously reported that mannitol strikingly increases blood flow to rat kidnevs hypoperfused at 35-40 mm Hg. This vasodilator effect is not due to volume expansion or alterations in plasma osmolality. We have tested the hypothesis that the vasodilatory effect of mannitol in the ischemic rat kidney is mediated by one of the vasoactive renal hormone systems: renin-angiotensin, kallikrein-kinin, or prostaglandins.Rats were infused with 5% mannitol in 0.9% saline to 3-5% of body weight. In agreement with our previous studies, RBF increased 1.3+0.1 ml/min despite maintenance of perfusion pressure at 35-40 mm Hg.The cyclooxygenase inhibitors, meclofenamate and indomethacin had no effect on renal blood flow (RBF) in hypoperfused kidneys. However, in rats pretreated with these inhibitors, expansion with mannitol increased RBF by only 0.37+0.02 ml/min, 28% of the response in the untreated group (P < 0.001). Infusion of prostacyclin (PGI2) into the renal artery during reduced perfusion resulted in an increase in RBF of 1.0+0.1 ml/min. Subsequent expansion with mannitol increased RBF by only 0.5±0.1 ml/min more, less than one-half of the effect of mannitol in a concurrent group of rats not treated with PGI2.Unlike PGI2, prostaglandin E2 had only a minimal vasodilator effect during hyperperfusion. Imidazole, an inhibitor of thromboxane synthesis, did not alter RBF or renal vascular resistance during hypoperfusion.Treatment of rats during hypoperfusion with the angiotensin-converting enzyme (kininase II) inhibitor teprotide increased RBF by 1.1±0.3 ml/min. However,

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Section: Discussionsupporting

confidence: 93%

Prostaglandins mediate the vasodilatory effect of mannitol in the hypoperfused rat kidney.

Johnston¹,

Bernard²,

Perrin³

et al. 1981

J. Clin. Invest.

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“…This is evidenced by enhanced ANG II-induced constriction during inhibition of cyclooxygenase (COX) with indomethacin (2,12,19,21,27,37 (15,33,35,56). To our knowledge, no in vivo studies to date have investigated the possibility of interactions during physiological conditions in which ANG II selectively increases RVR independently of changes in systemic AP.…”

mentioning

confidence: 99%

Short-term ANG II produces renal vasoconstriction independent of TP receptor activation and TxA₂/isoprostane production

Vågnes¹,

Iversen²,

Arendshorst³

2007

American Journal of Physiology-Renal Physiology

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The relative contributions of vasoconstrictor and of dilator systems are balanced in health. The balance is reset in disease, often favoring a predominant role of vasoconstrictors, perhaps due to positive interactions between constrictor systems. For example, in hypertension, chronic high levels of angiotensin II (ANG II) stimulate the production of thromboxane (TxA 2/PGH2) and/or isoprostane that activate constrictor thromboxane prostanoid (TP) receptors in the vasculature. The present study evaluated a modest concentration of ANG II administered acutely into the renal artery on urinary excretion of TxB 2 and isoprostane and possible renal TP receptor activation that might amplify ANG IIinduced renal vasoconstriction. TP receptors were blocked with SQ29548 coinfused with ANG II. Results were compared with a time control group of continuous ANG II infusion (40 ng ⅐ min Ϫ1 ⅐ kg body wt Ϫ1 ) over 90 min. TP receptor antagonism during 30 -60 min had no effect on the reduction in renal blood flow (RBF) produced by ANG II (15.8 Ϯ 2.8 vs. 13.2 Ϯ 4.9%) (P Ͼ 0.6). Likewise, there was no difference between groups during ANG II-induced renal vasoconstriction between 60 -90 min in presence or absence of TP receptor antagonist (RBF Ϫ8.6 Ϯ 4.0 vs. Ϫ9.6 Ϯ 4.5%) (P Ͼ 0.8). Systemic arterial pressure was stable throughout, so RBF changes reflected localized changes in renal vascular resistance. Urinary excretion of TxB2 and isoprostane were nearly doubled by ANG II. The present data indicate that short-term intrarenal infusion of ANG II rapidly increases renal production of TxA2 but that the ANG II-induced renal vasoconstriction is independent of TP receptor activation during the initial 90 min of local challenge with ANG II. kidney; renal circulation; glomerular arterioles; renin-angiotensin system; prostanoids; oxidative stress; isoprostane RENAL HEMODYNAMIC REGULATORY mechanisms play an important role in maintaining glomerular function, salt and water balance, and arterial pressure (AP). Renal vascular resistance (RVR) is controlled by a balance of vasoconstrictor and dilatory stimuli in health, with the vasoconstrictor agents predominating in many disease states. For example, in genetic hypertension in the spontaneously hypertensive rat (SHR), exaggerated renal vasoconstriction is seen in response to ANG II, a response primarily due to defective buffering of vasodilator prostanoids (12,14,24,40). On the other hand, higher expression of a G protein-coupled receptor such as thromboxane prostanoid (TP) and vasopressin (V 1 ) receptors can account for the ability of thromboxane A 2 (TxA 2 ) and vasopressin, respectively, to produce more pronounced renal vasoconstriction in young SHR (11,13,18,48). In long-standing established hypertension, there are significant potentiating interactions among vasoconstrictor systems. In this regard, chronic increases in ANG II are known to stimulate production of TxA 2 /PGH 2 with subsequent constriction-mediated TP receptors as well as angiotensin AT 1 receptors. In ANG II-induced hypertension...

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“…angiotensin system, the prostaglandins, nitric oxide, endothelin nor renal nerves seem to play a major role in autoregulation of RBF and GFR in the normal rat [1][2][3][4] In several models of renal disease, RBF autoregulation is markedly different from what is seen in the normal animal. In the remnant-kidney model, and in rats with end-stage glomerulonephritis, autoregulation of the RBF is absent [5,6].…”

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confidence: 99%

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

Kvam

Ofstad

Iversen³

2000

Kidney Blood Press Res

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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.

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Effect of prostaglandin synthetase inhibitors on renal blood flow in the rat

Cited by 56 publications

References 0 publications

Prostaglandins mediate the vasodilatory effect of mannitol in the hypoperfused rat kidney.

Prostaglandins mediate the vasodilatory effect of mannitol in the hypoperfused rat kidney.

Short-term ANG II produces renal vasoconstriction independent of TP receptor activation and TxA₂/isoprostane production

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

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Effect of prostaglandin synthetase inhibitors on renal blood flow in the rat

Cited by 56 publications

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Prostaglandins mediate the vasodilatory effect of mannitol in the hypoperfused rat kidney.

Prostaglandins mediate the vasodilatory effect of mannitol in the hypoperfused rat kidney.

Short-term ANG II produces renal vasoconstriction independent of TP receptor activation and TxA2/isoprostane production

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

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Short-term ANG II produces renal vasoconstriction independent of TP receptor activation and TxA₂/isoprostane production