Bradykinin causes selective efferent arteriolar dilation during angiotensin I converting enzyme inhibition

Kon, Valentina; Fogo, Agnes B.; Ichikawa, Iekuni; Hellings, Samuel; Bills, Teresa

doi:10.1038/ki.1993.279

Cited by 193 publications

(115 citation statements)

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“…When the differential pharmacological mechanisms of the 2 classes of agents are compared, the issues concerning the effects of bradykinin and angiotensin type 2 receptor have been raised. It is well known that ACE inhibition results in reduced degradation of bradykinin 6,7 and that bradykinin may cause selective efferent arteriolar dilatation 26 and stimulate endothelial NO formation. This action could provide reverse glomerular capillary hypertension and additional amelioration of renal injury.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin Type 1 Receptor Antagonism and ACE Inhibition Produce Similar Renoprotection in N ^ω -Nitro- l >-Arginine Methyl Ester/Spontaneously Hypertensive Rats

et al. 2001

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Abstract-This study was conducted to determine potentially differential effects between an angiotensin II type 1 (AT 1 ) receptor antagonist and an ACE inhibitor on systemic, renal, and glomerular hemodynamics and pathological changes in spontaneously hypertensive rats (SHR) with N -nitro-L-arginine methyl ester (L-NAME)-exacerbated nephrosclerosis. The hemodynamic, renal micropuncture, and pathological studies were performed in 9 groups of 17-week-old male SHR treated as follows: group 1, controls (nϭ16); group 2, candesartan (10 mg/kg per day for 3 weeks) (nϭ7); group 3, enalapril (30 mg/kg per day for 3 weeks) (nϭ8); group 4, candesartan (5 mg/kg per day) plus enalapril (15 mg/kg per day for 3 weeks) (nϭ9); group 5, L-NAME (50 mg/L in drinking water for 3 weeks) (nϭ17); group 6, L-NAME (50 mg/L) plus candesartan (10 mg/kg per day for 3 weeks) (nϭ7); group 7, L-NAME (50 mg/L) for 3 weeks followed by candesartan (10 mg/kg per day) for another 3 weeks (nϭ8); group 8, L-NAME (50 mg/L) plus enalapril (30 mg/kg per day for 3 weeks) (nϭ7); and group 9, L-NAME (50 mg/L) plus enalapril (30 mg/kg per day) and the bradykinin antagonist icatibant (500 g/kg SC per day via osmotic minipump for 3 weeks) (nϭ7). Both candesartan and enalapril similarly reduced mean arterial pressure and total peripheral resistance index. These changes were associated with significant decreases in afferent and efferent glomerular arteriolar resistances as well as glomerular capillary pressure. Histopathologically, the glomerular and arterial injury scores were decreased significantly, and left ventricular and aortic masses also were diminished significantly in all treated groups. L-NAME-induced urinary protein excretion was prevented by both candesartan and enalapril. Thus, both AT 1 receptor and ACE inhibition prevented and reversed the pathophysiological alterations of L-NAME-exacerbated nephrosclerosis in SHR. Itatibant only blunted the antihypertensive effects of enalapril but did not attenuate the beneficial effects of ACE inhibition on the L-NAME-induced nephrosclerosis. Thus, the AT 1 receptor antagonism and ACE inhibition have similar renal preventive effects, which most likely were achieved through reduction in the effects of angiotensin II, and ACE inhibition of bradykinin degradation demonstrated little evidence of renoprotection. (Hypertension. 2001;37:1262-1267.)

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Section: Discussionmentioning

confidence: 99%

Angiotensin Type 1 Receptor Antagonism and ACE Inhibition Produce Similar Renoprotection in N ^ω -Nitro- l >-Arginine Methyl Ester/Spontaneously Hypertensive Rats

et al. 2001

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“…There is also evidence from studies with bradykinin antagonists suggesting that bradykinin can contribute to the renal effects of ACE inhibition alone (Kon et al, 1993;Bouaziz et al, 1994) and EP 24.11 inhibition alone (Ura et al, 1994). We tested the effects of the bradykinin B2-receptor antagonist Hoe 140 on the systemic haemodynamic and renal effects of combined inhibition of ACE and EP 24.11.…”

Section: Effects Of Hoe 140 In Conscious Rabbitsmentioning

confidence: 99%

Role of bradykinin receptors in the renal effects of inhibition of angiotensin converting enzyme and endopeptidases 24.11 and 24.15 in conscious rabbits

Tomoda

Lew

Smith

et al. 1996

British J Pharmacology

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1 We tested the effects on systemic haemodynamics and renal function, of inhibition of endopeptidase (EP) 24.15 (E.C. 3.4.24.15), in conscious uninephrectomized rabbits in which the activities of angiotensin converting enzyme (ACE, E.C. 3.4.15.1) and neutral endopeptidase (EP 24.11, E.C. 3.4.24.11) were already inhibited. To test the role of bradykinin B2-receptors in mediating the effects following inhibition of these enzymes, the antagonist Hoe 140 was used. 2 Hoe 140 (0.1 mg kg-', i.v.) did not affect resting mean arterial pressure or heart rate, but antagonized the depressor effect of right atrial administration of bradykinin. The dose-response curve for bradykinin was shifted more than 1000 fold to the right for more than 4 h. Hoe 140 approximately doubled resting urine flow and increased fractional Na+ excretion from 4.2 to 6.0%; consistent with the hypothesis that it exerts a partial agonist effect on the kidney.3 Combined inhibition of ACE (captopril; 0.25 mg kg-' plus 0.2 mg kg-'h-') and EP 24.11 (SCH 39370; 3 mg kg-' plus 3 mg kg-'h-') was followed by a sustained reduction in arterial pressure (-6+ 2 mmHg) and increase in heart rate (35+7 beats min-'). There was a small increase in renal blood flow (by 6.5+3.2% relative to vehicle-treatment) without a change in glomerular filtration rate, and about a 150% increase in Na+ excretion. Hoe 140 (0.1 mg kg-', i.v.) pretreatment did not influence the renal effects of captopril and SCH 39370, although it did appear to blunt their hypotensive and tachycardic effects.4 When EP 24.15 was inhibited with N-[l-(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Tyr-p-aminobenzoate (cFP-AAY-pAB; 5 mg kg-' plus 3 mg kg-'h-', i.v.) in rabbits pretreated with captopril and SCH 39370, no changes in systemic haemodynamics or renal function were observed. 5 We concluded that in conscious uninephrectomized rabbits, EP 24.15 does not play a major role in modulating renal function, at least under conditions where ACE and EP 24.11 are already inhibited. In contrast, ACE and/or EP 24.11 do modulate renal function in this model, but their influences are mediated chiefly through metabolism of peptides other than bradykinin.

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“…16 Furthermore, the reduction in glomerular capillary pressure produced by an ACE-I has been shown to be significantly inhibited by treatment with a kinin receptor antagonist. 17 Conversely, long-term coadministration of a kinin receptor blocker did not decrease the beneficial effects of an ACE-I after 5/6 nephrectomy. 18 …”

Section: Angiotensin II As An Effector In Progressive Glomerulosclerosismentioning

confidence: 95%

ACE-I vs angiotensin II receptor antagonists: prevention of renal injury in chronic rat models

Brenner

1999

J Hum Hypertens

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There is now abundant evidence that treatment with angiotensin-converting enzyme inhibitors (ACE-I) ameliorates the progression of chronic renal disease. Attention has therefore focused on the role of the renin angiotensin-aldosterone (RAA) system in mediating the development of progressive glomerulosclerosis and angiotensin II (Ang II) has been implicated in several processes thought to be important in the pathogenesis of this entity. Conversely, ACE is also known to catalyse the breakdown of bradykinin. Thus, ACE-I treatment results in elevated bradykinin levels which may cause selective efferent arteriolar dilatation, suggesting an alternative explanation for the beneficial effects of this class of drugs in chronic renal disease. The development of specific angiotensin type 1 receptor antagonists (AT 1 RA) has provided a means of testing the relative

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Bradykinin causes selective efferent arteriolar dilation during angiotensin I converting enzyme inhibition

Cited by 193 publications

References 30 publications

Angiotensin Type 1 Receptor Antagonism and ACE Inhibition Produce Similar Renoprotection in N ^ω -Nitro- l >-Arginine Methyl Ester/Spontaneously Hypertensive Rats

Angiotensin Type 1 Receptor Antagonism and ACE Inhibition Produce Similar Renoprotection in N ^ω -Nitro- l >-Arginine Methyl Ester/Spontaneously Hypertensive Rats

Role of bradykinin receptors in the renal effects of inhibition of angiotensin converting enzyme and endopeptidases 24.11 and 24.15 in conscious rabbits

ACE-I vs angiotensin II receptor antagonists: prevention of renal injury in chronic rat models

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Bradykinin causes selective efferent arteriolar dilation during angiotensin I converting enzyme inhibition

Cited by 193 publications

References 30 publications

Angiotensin Type 1 Receptor Antagonism and ACE Inhibition Produce Similar Renoprotection in N ω -Nitro- l >-Arginine Methyl Ester/Spontaneously Hypertensive Rats

Angiotensin Type 1 Receptor Antagonism and ACE Inhibition Produce Similar Renoprotection in N ω -Nitro- l >-Arginine Methyl Ester/Spontaneously Hypertensive Rats

Role of bradykinin receptors in the renal effects of inhibition of angiotensin converting enzyme and endopeptidases 24.11 and 24.15 in conscious rabbits

ACE-I vs angiotensin II receptor antagonists: prevention of renal injury in chronic rat models

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Product

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Angiotensin Type 1 Receptor Antagonism and ACE Inhibition Produce Similar Renoprotection in N ^ω -Nitro- l >-Arginine Methyl Ester/Spontaneously Hypertensive Rats

Angiotensin Type 1 Receptor Antagonism and ACE Inhibition Produce Similar Renoprotection in N ^ω -Nitro- l >-Arginine Methyl Ester/Spontaneously Hypertensive Rats