Effect of exogenous and endogenous angiotensin II in the isolated perfused rat kidney

Dávalos, M; Frega, Norberto; Saker, B.; Leaf, Alexander

doi:10.1152/ajprenal.1978.235.6.f605

Cited by 44 publications

(27 citation statements)

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“…Both hindquarters were isolated by sectioning the animal at the level in which the perfusion cannula was introduced. During the initial 8-10 min of perfusion, the preparation was thoroughly rinsed with 2 liter of saline at 37°C while being perfused with 500 ml of modified KrebsHenseleit solution at 37°C, gassed with 02/CO2 (95%/5%) and containing 90 mg/100 ml glucose and 4% bovine serum albumin (Fraction V, Miles Laboratories, Inc., Elkhart, IN) and 2.4 mM phosphate (16). During this initial washing period the flow was adjusted to obtain a perfusion pressure of =60 mmHg and the effluent exiting from the vena cava was discarded.…”

Section: Methodsmentioning

confidence: 99%

Local generation of angiotensin II as a mechanism of regulation of peripheral vascular tone in the rat.

Oliver¹,

Sciacca²

1984

J. Clin. Invest.

114

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Abstract. Renin is present in vascular smooth muscle cells and has been shown to coexist with angiotensins I (Al) and II (All) in many cell types. Accordingly, we postulated that the renin-angiotensin system controls vascular tone, not by the action of circulating renal renin but rather, by the local generation of angiotensin by vascular renin. Isolated rat hindquarters were perfused in vitro with Krebs-Henseleit buffer containing 7% albumin, and flow-adjusted to obtain a perfusion pressure of -90 mmHg. Infusion of 4.8 nmol* min-' for 5 min of All or Al markedly increased perfusion pressure. An identical dose of the synthetic tetradecaptide of renin substrate (TDCP-RS) increased pressure similarly to Al. The pressure increase evoked by TDCP-RS was markedly decreased by captopril and by two different peptides that inhibit renin. Renin activity in the perfusate, incubated with semipurified rat renin substrate, was 21±3 pg Al ml-' h-' (mean±SEM) at 15 min of perfusion and 47±4 pg Al -ml-' -h-' at 45 min (n = 9; P < 0.01). When TDCP-RS was infused at 4.8 nmol * min-' for 5 min in the presence of captopril, Al in the perfusate increased linearly at a rate of 16.5 pmol min-' for 10 min (n = 5). The results indicate that TDCP-RS constricted the vasculature by its conversion to All and suggest that All was generated from a two-step hydrolysis of TDCP-RS by renin and converting enzyme. The data thus suggest that the renin-angiotensin system controls vascular tone by the local generation of All by renin and converting enzyme in the vasculature.

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Section: Methodsmentioning

confidence: 99%

Local generation of angiotensin II as a mechanism of regulation of peripheral vascular tone in the rat.

Oliver¹,

Sciacca²

1984

J. Clin. Invest.

114

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“…A number of studies have examined the role ofangiotensin II (Ang II), ' the physiologically active component of the system, in the control ofrenal hemodynamics as well as its sites ofaction within the kidney ( 1 ). Infusion ofAng II or inhibition of its action in the kidney has been shown to result in an increased or decreased filtration fraction, respectively (2)(3)(4)(5). Thus it has been postulated that sensitivity to Ang II is higher in the postglomerular efferent (Ef) than in the preglomerular afferent (Af) arteriole (Art).…”

Section: Introductionmentioning

confidence: 99%

Endothelium-derived relaxing factor/nitric oxide modulates angiotensin II action in the isolated microperfused rabbit afferent but not efferent arteriole.

Ito¹,

Arima²,

Ren³

et al. 1993

J. Clin. Invest.

181

104

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It has been reported that sensitivity to angiotensin II (Ang II) is higher in efferent (Ef) than afferent (Af) arterioles (Arts). We tested the hypothesis that this is due to arteriolar differences in the interaction between Ang II and endothelium-derived relaxing factor/nitric oxide (EDNO). Rabbit Af-Arts with glomerulus intact were microperfused in vitro at a constant pressure. Ef-Arts were perfused from the distal end of either the Af-Art (orthograde perfusion) or the Ef-Art (retrograde perfusion) to eliminate influences of the Af-Art or glomerulus, respectively. Ang II did not alter Af-Art luminal diameter until the concentration reached 10-9 M, which decreased the diameter by 11±2.6% (n = 11; P < 0.002). In contrast, Ef-Arts became significantly constricted at concentrations as low as 10-11 M with either perfusion. Surprisingly, the decrease in Ef-Art diameter at 10-10, 10-', and 10-8 M was significantly greater with retrograde perfusion (44±6.9%, 70±5.6%, and 74±4.1%, respectively; n = 5) than with orthograde perfusion (16±4.2%, 25±2.9%, and 35±3.5%; n = 9). ENDO synthesis inhibition with 10-4 M nitro-L-arginine methyl ester (L-NAME) decreased the diameter to a greater extent in Af-Arts (22±3.0%; n = 11 ) compared to Ef-Arts with either orthograde (9.5±2.3%; n = 8) or retrograde perfusion (1.2±2.1%; n = 6). With L-NAME pretreatment, Af-Art constriction induced by 10-10 M (14±4.0%, n = 9) and 10-9 M Ang 11 (38±3.9%) was significantly greater compared to nontreated Af-Arts. In contrast, L-NAME pretreatment had no effect on Ang II-induced constriction in Ef-Arts with either perfusion. In conclusion, this study demonstrates higher sensitivity of Ef-Arts to Ang II, particularly with retrograde perfusion. Our results suggest that EDNO significantly modulates the vasoconstrictor action of Ang II in Af-Arts II but not Ef-Arts, contributing to the differential sensitivity

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“…Angiotensin II (AII) is a strong vasoconstrictor hormone of the afferent and the efferent arterioles in the kidney (8). The decrease in perfusate flow by AII in the isolated kidney is well documented (8,11,(15)(16)(17) (weight, 350 to 450 g) were used as kidney donors for the isolated perfused rat kidney preparations. All animals were allowed free access to food and water before experimentation.…”

mentioning

confidence: 99%

Influence of angiotensin II-induced alterations in renal flow on excretion of cefonicid in isolated perfused rat kidneys

Rodríguez

Smith

1992

Antimicrob Agents Chemother

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The effects of variations in renal perfusate flow on the excretion of cefonicid was examined in isolated perfused rat kidneys. Cefonicid, an expanded-spectrum cephalosporin, is primarily eliminated by active tubular secretion and is neither metabolized nor reabsorbed in the isolated kidney. We used angiotensin II (All), a strong vasoconstrictor hormone of the afferent and the efferent arterioles in the kidney, to determine whether the renal and secretion clearances, as well as the excretion ratio (ER = CLR/I[I X GFRJ, where CLR is renal clearance, f. is the unbound fraction, and GFR is glomerular filtration rate), of this low-extraction compound can be altered by a decreased perfusion flow. Control studies were performed in the absence (n = 5) and presence (n = 4) of All; cefonicid studies were performed in the absence (n = 4) and presence (n = 5) ofAII. AII (1 to 4 ng/min) and cefonicid (5 to 10 p.g/min) were infused into the perfusate. Cefonicid was assayed by high-performance liquid chromatography, and its protein binding was determined by ultrafiltration. AII decreased the perfusate flow rate and increased the renal vascular resistance and filtration fraction of the isolated kidney in the presence and absence of cefonicid. The glomerular filtration rate remained unchanged among the groups. The fractional excretion of glucose was low and steady, indicating a well-preserved tubular function. Although the unbound fraction was unchanged between treatments, the renal and secretion clearances and the excretion ratio of cefonicid were reduced by about 40%o in the presence of All (excretion ratios, 10.3 without AII versus 6.03 with All). These results suggest that the altered clearance parameters of cefonicid are the result of a flow-induced change in the intrinsic secretory transport of the drug.A major factor in the ability of an organ to remove a compound from the circulation is the rate at which the compound is delivered to the organ. The effect of flow rate on this drug removal process is critical, especially for those drugs in which the difference between the arterial and venous concentrations across the organ is very high (i.e., drugs with a high extraction ratio). However, the ability of disease to cause blood flow-induced changes in the hepatic clearance of low-extraction drugs has also been established (19,22). Hence, it is relevant to consider whether the relationships between clearance and organ flow that operate for drug elimination from the liver apply as well for renal drug elimination.The utility of the isolated perfused rat kidney in the evaluation of the disposition of compounds has been shown previously (3,21). Isolated organs enable the study of renal function under states in which variables can be carefully and systematically changed (13,14). Cefonicid, an expandedspectrum cephalosporin, is 96% bound in humans (at 100 p,g/mL), is actively secreted, and is neither metabolized nor reabsorbed in the isolated kidney (20a). In addition, cefonicid is a compound of low renal extraction in the isolated ...

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Effect of exogenous and endogenous angiotensin II in the isolated perfused rat kidney

Cited by 44 publications

References 0 publications

Local generation of angiotensin II as a mechanism of regulation of peripheral vascular tone in the rat.

Local generation of angiotensin II as a mechanism of regulation of peripheral vascular tone in the rat.

Endothelium-derived relaxing factor/nitric oxide modulates angiotensin II action in the isolated microperfused rabbit afferent but not efferent arteriole.

Influence of angiotensin II-induced alterations in renal flow on excretion of cefonicid in isolated perfused rat kidneys

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