Renal Hemodynamic Effects of Nonhypotensive Doses of Angiotensin-Converting Enzyme Inhibitors in Hypertension and Heart Failure Rats

Nelissen-Vrancken, H. J. M. G.; Struijker‐Boudier, Harry A.J.; Smits, J. F. M.

doi:10.1097/00005344-199202000-00002

Cited by 15 publications

(9 citation statements)

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“…To determine the renal effects of captopril–lysozyme, we measured renal haemodynamics and sodium excretion after 6 h of treatment. To exclude the effect of systemic haemodynamics on these parameters, dosages of free captopril were used that did not significantly affect blood pressure (Nelissen Vrancken et al ., 1992). ERPF was moderately decreased after 6 h of treatment in both vehicle and lysozyme‐treated rats due to the frequent sampling of blood (−14.9±3.2% and −16.3±2.8%, respectively; P <0.05 vs pre‐treatment values) (de vries et al ., 1997).…”

Section: Resultsmentioning

confidence: 99%

Renal targeting of captopril selectively enhances the intrarenal over the systemic effects of ACE inhibition in rats

Haverdings

Haas

Navis

et al. 2002

British J Pharmacology

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1 In previous studies on the renal targeting of the ACE inhibitor captopril, we demonstrated that a 6 fold increased concentration of this drug could be obtained in the kidney after conjugation to the low-molecular-weight protein lysozyme. In this study, we investigated in unrestrained rats whether systemic administration of captopril ± lysozyme also results in an enhanced e ect on renal parameters, relative to the systemic e ects.2 Renal e ects: intravenous infusion of captopril ± lysozyme for 6 h resulted in a more pronounced increment of renal blood¯ow (31+2% vs 17+4% at 0.5 mg kg 71 6h 71 , P50.01) and an approximately 5 fold enhanced natriuresis (167+17% vs 36+7% at 1 mg kg 71 6 h 71 , P50.001) in comparison with equimolar amounts of captopril as a free drug. In correspondence with these ®ndings, renal ACE inhibition was potentiated approximately 5 fold (750+4% vs 722+3% at 1 mg kg 71 6 h 71 , P50.001).3 Systemic e ects: conjugated captopril did not a ect blood pressure in dosages up to 5 mg kg 71 6 h 71 . This e ect coincided with a less pronounced inhibition of the pressor response to intravenously administered angiotensin I (712+3% vs 766+5% at 1 mg kg 71 6 h 71 , P50.001), and a markedly attenuated plasma ACE inhibition (719+2% vs 737+3% at 1 mg kg 71 6 h 71 , P50.001) compared to an equivalent dose of free captopril. 4 An experiment of continued intravenous administration of captopril ± lysozyme for 7 days in nephrotic syndrome demonstrated that the conjugate is also active in renal disease: the antiproteinuric response was substantially augmented (767+5% vs 715+7% at 4 mg kg 71 24 h 71 , P50.001) compared to the free drug, in the absence of blood pressure reduction. 5 These data demonstrate that intravenous administration of a captopril ± lysozyme conjugate leads to more selective renal ACE inhibition and enhanced renal e ects as well as less systemic e ects compared to captopril itself.

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Section: Resultsmentioning

confidence: 99%

Renal targeting of captopril selectively enhances the intrarenal over the systemic effects of ACE inhibition in rats

Haverdings

Haas

Navis

et al. 2002

British J Pharmacology

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“…The dose range was chosen based on previous experience (Nelissen‐Vrancken et al . ). On the same day, after a 60–120 min recovery period, bolus doses of PE of 20, 200, 500, 1000 and 1500 ng kg –1 were injected in volumes of 100 μl at 5 min intervals.…”

Section: Methodsmentioning

confidence: 97%

“…Averages of the last 2 s before the next step were used to calculate P O 2 and mean arterial pressure (MAP). The dose range was chosen based on previous experience (Nelissen-Vrancken et al 1992). On the same day, after a 60-120 min recovery period, bolus doses of PE of 20, 200, 500, 1000 and 1500 ng kg -1 were injected in volumes of 100 μl at 5 min intervals.…”

Section: Effects Of Angiotensin II and Phenylephrine On Renal Corticamentioning

confidence: 99%

“…Together this probably explains why PE did not significantly reduce cortical P O 2 . Furthermore, renal resistance was reduced and RBF increased after a non-hypotensive dose of captopril in healthy conscious rats (Nelissen-Vrancken et al 1992), suggesting, although not decisively, that RAS inhibition could increase renal tissue P O 2 by increasing D O 2 . The maintenance ofQ O 2 during infusion of AngII is probably due to the maintenance of GFR (as reflected in increased FF), and thus the filtered load of sodium.…”

Section: Figure 5 Responses To Intravenous Infusions Of Angiotensin-mentioning

confidence: 99%

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Exogenous and endogenous angiotensin‐II decrease renal cortical oxygen tension in conscious rats by limiting renal blood flow

Emans

Janssen

Pinkham

et al. 2016

The Journal of Physiology

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Key points Our understanding of the mechanisms underlying the role of hypoxia in the initiation and progression of renal disease remains rudimentary.We have developed a method that allows wireless measurement of renal tissue oxygen tension in unrestrained rats.This method provides stable and continuous measurements of cortical tissue oxygen tension (PO2) for more than 2 weeks and can reproducibly detect acute changes in cortical oxygenation.Exogenous angiotensin‐II reduced renal cortical tissue PnormalO2 more than equi‐pressor doses of phenylephrine, probably because it reduced renal oxygen delivery more than did phenylephrine.Activation of the endogenous renin–angiotensin system in transgenic Cyp1a1Ren2 rats reduced cortical tissue PnormalO2; in this model renal hypoxia precedes the development of structural pathology and can be reversed acutely by an angiotensin‐II receptor type 1 antagonist.Angiotensin‐II promotes renal hypoxia, which may in turn contribute to its pathological effects during development of chronic kidney disease. AbstractWe hypothesised that both exogenous and endogenous angiotensin‐II (AngII) can decrease the partial pressure of oxygen (PO2) in the renal cortex of unrestrained rats, which might in turn contribute to the progression of chronic kidney disease. Rats were instrumented with telemeters equipped with a carbon paste electrode for continuous measurement of renal cortical tissue PnormalO2. The method reproducibly detected acute changes in cortical oxygenation induced by systemic hyperoxia and hypoxia. In conscious rats, renal cortical PnormalO2 was dose‐dependently reduced by intravenous AngII. Reductions in PnormalO2 were significantly greater than those induced by equi‐pressor doses of phenylephrine. In anaesthetised rats, renal oxygen consumption was not affected, and filtration fraction was increased only in the AngII infused animals. Oxygen delivery decreased by 50% after infusion of AngII and renal blood flow (RBF) fell by 3.3 ml min−1. Equi‐pressor infusion of phenylephrine did not significantly reduce RBF or renal oxygen delivery. Activation of the endogenous renin–angiotensin system in Cyp1a1Ren2 transgenic rats reduced cortical tissue PnormalO2. This could be reversed within minutes by pharmacological angiotensin‐II receptor type 1 (AT1R) blockade. Thus AngII is an important modulator of renal cortical oxygenation via AT1 receptors. AngII had a greater influence on cortical oxygenation than did phenylephrine. This phenomenon appears to be attributable to the profound impact of AngII on renal oxygen delivery. We conclude that the ability of AngII to promote renal cortical hypoxia may contribute to its influence on initiation and progression of chronic kidney disease.

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“…Furthermore, the RAAS is activated in human heart failure (Dube & Weber, 2011). Pharmacological attenuation of the RAAS suggests that Ang II continuously regulates the renal, but not mesenteric or hindquarter, blood flow and vascular resistance of healthy rats and those with heart failure induced by myocardial infarction (Nelissen-Vrancken et al 1992;Mento et al 1996). Angiotensin II acting on Ang II type 1 (AT 1 ) receptors also appears continuously to regulate the renal blood flow and vascular resistance of rats with aortocaval fistula shortly after fistula creation (Brodsky et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II control of regional haemodynamics in rats with aortocaval fistula

Duggan

Tabrizchi

2016

Experimental Physiology

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New Findings r What is the central question of this study?Hyperdynamic circulation because of arteriovenous fistula results in reduction of blood flow to organs but is a model of low circulatory resistance with activated renin-angiotensin system. The aim was to determine contributions of different subtypes of angiotensin II receptors to regional blood flow and vascular conductance in a hyperdynamic circulatory state. r What is the main finding and its importance?The renin-angiotensin system plays a pivotal role in control of regional blood flow in animals with arteriovenous fistula and makes a major contribution to the maintenance of normal arterial blood pressure. In this hyperdynamic circulatory state model, angiotensin II type 1 receptors predominated in regulating regional haemodynamics.Regional perfusion is reduced and the renin-angiotensin system activated in rats with aortocaval fistula. The effects of captopril (angiotensin-converting enzyme inhibitor), losartan (angiotensin II type 1 receptor antagonist) and PD 123319 (angiotensin II type 2 receptor antagonist) on regional blood flow and vascular conductance were assessed in rats with aortocaval fistula and sham-operated rats. Control of blood flow and vascular conductance by angiotensin II was evaluated by serial bolus injections of captopril, losartan and PD 123319 in anaesthetized rats. In rats with fistula, PD 123319 significantly decreased, whereas captopril and losartan increased, mesenteric blood flow. The decrease in mesenteric blood flow induced by PD 123319 was significantly greater in rats with fistula compared with sham operation. Captopril and PD 123319 significantly decreased renal blood flow compared with losartan, which increased it. In sham-operated rats, captopril and losartan significantly increased, whereas PD 123319 decreased, mesenteric and renal conductance. In rats with fistula, captopril and losartan significantly increased, whereas PD 123319 decreased, mesenteric conductance. The significant increase produced by losartan on mesenteric conductance was greater in rats with fistula compared with sham operation. PD 123319 produced a significantly greater decrease in renal conductance of rats with aortocaval fistula compared with sham-operated rats. Captopril, losartan and PD 123319 did not significantly affect perfusion in the hindquarter in rats with fistula or sham-operated. The renin-angiotensin system is more active in the control of regional haemodynamics in rats with aortocaval fistula and acts as a mechanism of maintaining normal arterial blood pressure in these animals. In rats with fistula, angiotensin II type 1 receptors predominate in regulating regional haemodynamics.

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Renal Hemodynamic Effects of Nonhypotensive Doses of Angiotensin-Converting Enzyme Inhibitors in Hypertension and Heart Failure Rats

Cited by 15 publications

References 0 publications

Renal targeting of captopril selectively enhances the intrarenal over the systemic effects of ACE inhibition in rats

Renal targeting of captopril selectively enhances the intrarenal over the systemic effects of ACE inhibition in rats

Exogenous and endogenous angiotensin‐II decrease renal cortical oxygen tension in conscious rats by limiting renal blood flow

Angiotensin II control of regional haemodynamics in rats with aortocaval fistula

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