The effect of indomethacin on autoregulation of renal blood flow in the anasthetized dog.

Beilin, L. J.; Bhattacharya, Jahar

doi:10.1113/jphysiol.1977.sp012018

Cited by 19 publications

(5 citation statements)

References 21 publications

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“…Remarkably, however, oscillations are easily visible in the time courses following both total and partial occlusions. This is in accord with many previous step response experiments (2,24,26,37,48,51,65). Values are mean Ϯ SE absolute values of mean arterial blood pressure (MABP), renal blood flow (RBF), renal conductance (RC), hindquarter blood flow (HQF), and hindquarter conductance (HQC) for n ϭ 13 rats under control conditions, after captopril bolus ͓angiotensin-converting enzyme inhibition (ACE-I)͔, and during angiotensin II (ANG II) clamp (coinfusion of captopril and ANG II).…”

Section: Resultssupporting

confidence: 80%

The renin-angiotensin system and the third mechanism of renal blood flow autoregulation

Seeliger¹,

Wronski²,

Ladwig³

et al. 2009

American Journal of Physiology-Renal Physiology

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Seeliger E, Wronski T, Ladwig M, Dobrowolski L, Vogel T, Godes M, Persson PB, Flemming B. The renin-angiotensin system and the third mechanism of renal blood flow autoregulation. Am J Physiol Renal Physiol 296: F1334 -F1345, 2009. First published April 1, 2009 doi:10.1152/ajprenal.90476.2008.-Autoregulation of renal blood flow comprises three mechanisms: the myogenic response (MR), the tubuloglomerular feedback (TGF), and a third mechanism (3M). The nature of 3M is unknown; it may be related to hypotensive resetting of autoregulation that probably relies on pressure-dependent stimulation of the renin-angiotensin system (RAS). Thus we used a normotensive angiotensin II clamp in anesthetized rats and studied autoregulation 1) by slow ramp-shaped reductions in renal perfusion pressure (RPP) followed by ramp-shaped RPP restorations and 2) by means of the step response technique: after 30 s of either total or partial suprarenal aortic occlusion, a step increase in RPP was made and the response of renal vascular conductance analyzed to assess the mechanisms' strength and initial direction (vasodilation or constriction). The angiotensin clamp abolished the resetting of autoregulation during ramp-shaped RPP changes. Under control conditions, the initial TGF response was dilatory after total occlusions but constrictive after partial occlusions. The initial 3M response presented a mirror image to the TGF: it was constrictive after total but dilatory after partial occlusions. The angiotensin clamp suppressed the TGF and turned the initial 3M response following total occlusions into dilation. We conclude that 1) pressure-dependent RAS stimulation is a major cause behind hypotensive resetting of autoregulation, 2) TGF sensitivity strongly depends on pressure-dependent changes in RAS activity, 3) the 3M is modulated, but not mediated, by the RAS, and 4) the 3M acts as a counterbalance to the TGF and might possibly be related to the recently described connecting tubule glomerular feedback. renal hemodynamics; time domain; oscillations; hindquarter CHANGES IN PERFUSION PRESSURE alter local blood flow by a variety of mechanisms. On one hand, changes in pressure result in passive circular stretching or destretching of vessels and thus in parallel changes in blood flow. On the other hand, via various pathways, pressure changes evoke active responses of vascular smooth muscles, i.e., vasoconstriction or vasodilation. First, pressure-induced flow changes result in metabolic changes in the tissue that, in turn, impinge on vascular muscles, as exemplified by the phenomenon of reactive hyperemia (5, 6). Second, flow changes alter shear stress, which impacts on vascular muscles, e.g., via altered release of nitric oxide (8). Third, in many vascular beds the phenomenon of blood flow autoregulation is observed, i.e., the ability to dampen or even to abolish the effects that changes in perfusion pressure would otherwise inevitably have on flow (16,35).Compared with blood flow control of other vascular beds, control of renal blood flow (RB...

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Section: Resultssupporting

confidence: 80%

The renin-angiotensin system and the third mechanism of renal blood flow autoregulation

Seeliger¹,

Wronski²,

Ladwig³

et al. 2009

American Journal of Physiology-Renal Physiology

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“…3), it is unlikely to have any direct impact on renal function, assuming that the autoregulatory capacity of the kidney remains intact. Beilin & Bhattacharya (1977) demonstrated that administration of indomethacin to anaesthetized dogs did not alter steady‐state autoregulation of RBF, although there was a transient decrease in RBF, as observed in the present experiments. We speculate that any sustained effects of indomethacin on RVR which could impact renal function, leading to oliguria if untreated, could only occur in the absence of the rapid buffering capacity we observed in the healthy newborn animal.…”

Section: Discussionsupporting

confidence: 76%

Effects of indomethacin on systemic and renal haemodynamics in conscious lambs

Ebenezar

Ghane

Smith

2007

Experimental Physiology

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Both prostaglandins (PGs) PGE 2 and PGI 2 can act as renal vasodilators, these effects being exacerbated when the renin-angiotensin system is activated. Therefore, we hypothesized that PGs would play a more predominant role in modulating renal haemodynamics in the newborn period, when the renin-angiotensin system is activated. To this end, the role of endogenously produced PGs in modulating systemic and renal haemodynamics was investigated in two groups of conscious lambs aged ∼1 and ∼6 weeks. Arterial pressure, venous pressure and renal blood flow were measured for 5 min before (control) and for 20 min after intravenous injection of vehicle (experiment 1). Twenty-four hours later, this protocol was repeated with intravenous injection of the non-selective cyclo-oxygenase inhibitor indomethacin (1 mg kg −1 , experiment 2). Heart rate was calculated from the systolic peak of the arterial pressure waveform, and renal vascular resistance (RVR) was calculated from the measured variables. In response to indomethacin but not vehicle, in both age groups of lambs there was an increase in mean arterial pressure and pulse interval, as well as a marked increase in RVR. These responses to indomethacin were, however, transient, with baseline levels being resumed within minutes. Although the hypothesis that PGs play a greater role in modulating renal haemodynamics early in life is not supported, these data do provide evidence that endogenously produced PGs modulate systemic and renal haemodynamics during postnatal maturation. It is apparent, however, that other vasoactive factors must be rapidly recruited in order to buffer the circulatory responses to removal of vasodilatory PGs in the developing newborn.

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“…Lawrie Beilin has made considerable contributions to hypertension in a research career spanning 40 years. He has published a range of important animal studies, including work in dogs, 1 rats 2 and rabbits, 3 but his primary focus has always been on human hypertension 4 …”

Section: Introductionmentioning

confidence: 99%

Species Variability in Cardiovascular Research: The Example of Adrenocorticotrophin‐induced Hypertension

Whitworth

Zhang

Mangos

et al. 2006

Clin Exp Pharma Physio

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1. Lawrie Beilin has contributed greatly to international hypertension research through both animal and human studies. 2. Animals are used in biomedical research to gain insights that can be extrapolated ultimately to humans. 3. A simple experimental manipulation, adrenocorticotrophin (ACTH) administration, has a range of different cardiovascular effects in different species. 4. Caution should be exercised in extrapolating data from animals to humans.

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The effect of indomethacin on autoregulation of renal blood flow in the anasthetized dog.

Cited by 19 publications

References 21 publications

The renin-angiotensin system and the third mechanism of renal blood flow autoregulation

The renin-angiotensin system and the third mechanism of renal blood flow autoregulation

Effects of indomethacin on systemic and renal haemodynamics in conscious lambs

Species Variability in Cardiovascular Research: The Example of Adrenocorticotrophin‐induced Hypertension

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