No effect of intrarenal converting enzyme inhibition on canine renal blood flow

Zimmerman, Ben G.; Wong, Pancras C.; Kounenis, G.; Kraft, E

doi:10.1152/ajpheart.1982.243.2.h277

Cited by 9 publications

(5 citation statements)

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“…These results are consistent with re cent findings in spontaneously hypertensive rats [Lappe et al, 1985] that converting en zyme inhibitors exerted graded regional va sodilation. Different responses of RBF and CBF or VBF to MC-838 or captopril may reflect that, first, the sensitivity for the vasoconstricting action of circulating All, which depends presumably on possible differences in receptor number, affinity and/or avail ability, is different among these vascular beds, as Fiksen-Olsen et al [1983] have re cently suggested; second, activities of angio tensin-converting enzyme located in the tar get organs such as the lung, kidney, heart and brain are not uniform [Polsky-Cynkin et al, 1980;Cohen and Kurz, 1982;Unger et al, 1985], A similar increase in RBF produced by captopril as seen in this study has been re ported in pentobarbital-anesthetized [Murthy et al, 1978;Satoh et al, 1980] and conscious dogs [Zimmerman et al, 1982]. Zimmerman et al [1982] have demonstrated that the increase in resting RBF by intravenous ad ministration of captopril can be accounted for a reduced level of circulating All through inhibition of angiotensin-converting en zyme.…”

Section: Discussionsupporting

confidence: 69%

Responses of Renal, Coronary and Vertebral Vasculatures to MC-838 and Captopril in Anesthetized Dogs

Noguchi¹,

Kato²,

Sunagawa³

et al. 1987

Pharmacology

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The regional hemodynamic effects of MC-838, a new angiotensin-converting enzyme inhibitor, and captopril at equidepressor doses were examined in the anesthetized dog by simultaneously measuring renal (RBF), coronary (CBF), vertebral (VBF) arterial and aortic blood flow (AoF). Hemodynamic responses to angiotensin I (AI), All and noradrenaline were compared before and after the administration of each inhibitor. MC-838 (3 mg/kg i.v.) lowered gradually aortic pressure (AoP) and increased moderately AoF and RBF up to 60 min after the administration. Captopril (0.1 mg/kg i.v.) lowered AoP immediately after the administration and increased AoF and RBF more shortly than MC-838. Neither inhibitor produced a marked change in VBF or CBF. The effects of the inhibitors in the renal vascular bed was much greater than that in vertebral and coronary vascular beds, although vascular resistance in all of them was significantly reduced. Each of the drugs inhibited the pressor and renal vasoconstrictor responses to AI. These results indicate that the renal vasculature is more sensitive to both MC-838 and captopril than vertebral and coronary vasculature, but MC-838 has a slower and longer-lasting action than does captopril.

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Section: Discussionsupporting

confidence: 69%

Responses of Renal, Coronary and Vertebral Vasculatures to MC-838 and Captopril in Anesthetized Dogs

Noguchi¹,

Kato²,

Sunagawa³

et al. 1987

Pharmacology

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“…Although the administration of renin inhibitors, ACE inhibitors or AT 1 receptor antagonists directly into the renal artery has been frequently applied to study the acute effects of intrarenal RAS inhibition, conflicting results have been obtained. Whereas in many studies RAS inhibition resulted in an increased renal blood flow and/or a stimulated natriuresis (Kimbrough et al ., 1977; Levens et al ., 1981a, 1983; Kastner et al ., 1984; Li & Zimmerman, 1987; Siragy et al ., 1990; Levens, 1990; Verburg et al ., 1990; Peng & Knox, 1995; Cervenka & Navar, 1999), other studies failed to demonstrate any effect on these parameters (Wong & Zimmerman, 1980; Zimmerman et al ., 1982; Zimmerman & Finis, 1985) or stated that renal haemodynamics are mainly influenced by circulating Ang II (Hall et al ., 1981; Kastner et al ., 1984; Rassier et al ., 1986). In addition, some studies used anaesthetized animals (Li & Zimmerman, 1987; Levens, 1990; Verburg et al ., 1990; Cervenka & Navar, 1999) or lacked appropriate controls to exclude extrarenal influences of these drugs (Kimbrough et al ., 1977; Levens et al ., 1981a).…”

Section: Discussionmentioning

confidence: 95%

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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“…In contrast to EXP 3174, administered directly intrare nally to avoid changes in MAP, we infused captopril intrave nously, since Zimmerman et al [19] showed that intrarenal administration of ACE inhibitors is unable to block the con version of Angl to Angll. As a result, we observed a de crease in MAP after captopril which was not the case with EXP 3174.…”

Section: Discussionmentioning

confidence: 99%

Comparative Effects of the Angiotensin II Receptor Blocker EXP 3174 and of the Angiotensin-Converting Enzyme Inhibitor Captopril on Renal Glomerular Hemodynamics in the Dog

Heller

Kramer²,

Horáček³

1997

Kidney Blood Press Res

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The effects on glomerular hemodynamics of angiotensin-converting enzyme (ACE) inhibition with captopril and of angiotensin II receptor blockade with EXP 3174, an active metabolite of losartan, either alone or in combination, were compared in anesthetized dogs. Administration of EXP 3174 intrarenally led to an increase in renal blood flow by +14% and in glomerular filtration rate by +7%, thus decreasing the filtration fraction by -5%. Similar changes were observed at the single-nephron level. Water, sodium, potassium, and urea excretion rates rose considerably. A decrease in effective filtration pressure by -27% and an increase in ultrafiltration coefficient, K_f, by +57% were seen. A drop in total arteriolar resistance by -19% was mainly due to a decrease in efferent (-25%) rather than afferent (-14%) resistance. When captopril, an ACE inhibitor, was administered intravenously after and during EXP 3174, an additional increase in renal blood flow, by +8%, with no change in glomerular filtration rate was seen which led to an additional decrease in filtration fraction by -5%; additional increases were observed in water and urea but not in sodium and potassium excretion rates. An additional decrease in total arteriolar resistance, by -14%, was now evenly distributed between the efferent (-6%) and afferent (-8%) arterioles. Almost all of these additional changes disappeared when a bradykinin B₂-antagonist, Hoe 140, was infused together with captopril. In conclusion, administration of an ACE inhibitor led to a significantly enhanced vasodilatory response in the kidney as compared with the administration of an angiotensin II receptor blocker. This enhancement was almost eliminated by the coadministration of Hoe 140, thus rendering the participation of kinins fairly plausible.

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No effect of intrarenal converting enzyme inhibition on canine renal blood flow

Cited by 9 publications

References 0 publications

Responses of Renal, Coronary and Vertebral Vasculatures to MC-838 and Captopril in Anesthetized Dogs

Responses of Renal, Coronary and Vertebral Vasculatures to MC-838 and Captopril in Anesthetized Dogs

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

Comparative Effects of the Angiotensin II Receptor Blocker EXP 3174 and of the Angiotensin-Converting Enzyme Inhibitor Captopril on Renal Glomerular Hemodynamics in the Dog

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