Mechanism of natriuretic action of bradykinin

Willis, Lynn R.; Ludens, JH; Jb, Hook; He, Weiling

doi:10.1152/ajplegacy.1969.217.1.1

Cited by 111 publications

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“…The renal effects of Hoe 140 more likely reflect its partial agonist property. This hypothesis is supported by the fact that the effects of Hoe 140 we observed, closely resemble those of intrarenally infused bradykinin (see Willis et al, 1969;Ader et al, 1992 Figure 5 Changes in renal Na + handling variables following treatment with the EP 24.15 inhibitor cFP-AAY-pAB, in rabbits pretreated with a combination of the ACE inhibitor, captopril and the EP 24.11 inhibitor, SCH 39370 and either the bradykinin antagonist Hoe 140 or its vehicle. Columns represent the mean changes from control levels (see Table 1) of each variable over 3 consecutive 20min periods (n=6-7).…”

Section: Effects Of Inhibition Of Ep 2415mentioning

confidence: 58%

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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Section: Effects Of Inhibition Of Ep 2415mentioning

confidence: 58%

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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“…Kinins are potent vasodilators, which acting as paracrine hormones, may be involved in the regulation of regional haemodynamics (Nolly et al, 1990;Saed et al, 1990;Wiemer et al, 1991;Gardiner et al, 1990;1992) and renal excretion of water and sodium (Willis et al, 1969;. Alteration of the function of locally formed kinins, leading to predominance of vasoconstrictor tone and retention of water and salt, may contribute to the pathogenesis of arterial hypertension.…”

Section: Introductionmentioning

confidence: 99%

Effects of Hoe 140, a bradykinin B₂‐receptor antagonist, on renal function in conscious normotensive rats

Madeddu

Anania

Demontis

et al. 1992

British J Pharmacology

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1. The present study was designed to determine if endogenous kinins are involved in the regulation of arterial blood pressure and renal function in conscious rats given deoxycorticosterone enantate (DOC, 25 mg kg-', s.c., weekly) or vehicle for two weeks. 2. The bradykinin B2-receptor antagonist, D-Arg[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin (Hoe 140), at a dose of 300 gg kg-', s.c., blocked the hypotensive effect of 300 ng kg-' bradykinin i.a., but it did not alter the blood pressure lowering action of 300 ng kg-' acetylcholine or prostaglandin E2. Inhibition of the response to bradykinin persisted up to 6 h after the administration of Hoe 140. 3. Administration of 300 fg kg-' Hoe 140 s.c. four times a day did not alter mean blood pressure, renal blood flow, or renal function in rats given DOC-vehicle. However, it decreased urinary volume by 70% (from 48.2 ± 3.8 to 14.3 ± 3.7 ml 24 h-', P<0.01) and urinary secretion of sodium by 54% (from 1.02 ± 0.05 to 0.47 ± 0.16 mmol 24 h-', P<0.01) and potassium by 30% (from 2.93 ± 0.15 to 2.04 ± 0.15 mmol 24 h-', P<0.05) in DOC-treated rats. Mean blood pressure, glomerular filtration rate and total renal blood flow remained unchanged. 4. Our results suggest that endogenous kinins play a role in the regulation of renal excretion of water and sodium in the presence of elevated levels of DOC.

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“…[1][2][3][4] They act as local hormones by activating specific receptors named B 1 and B 2 , with most of the cardiovascular and renal effects being mediated by the B 2 receptor. 5 It has been hypothesized that a dysfunction of the KKS, leading to unbalanced predominance of vasoconstrictor and antinatriuretic systems, may contribute to the pathogenesis of arterial hypertension.…”

mentioning

confidence: 99%

Enhanced Blood Pressure Sensitivity to Deoxycorticosterone in Mice With Disruption of Bradykinin B ₂ Receptor Gene

Emanueli

Fink²,

Milia³

et al. 1998

Hypertension

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Abstract-The renal kallikrein-kinin system is activated under conditions of mineralocorticoid excess. To evaluate whether endogenous kinins exert a protective role against the development of mineralocorticoid-induced hypertension, we studied the cardiovascular effects induced by long-term administration of deoxycorticosterone (DOC; 0.3 mol/g body wt SC once per week for 6 weeks) or vehicle in transgenic mice (Bk2r Ϫ/Ϫ ) lacking the bradykinin B 2 receptor gene and in wild-type controls (Bk2r ϩ/ϩ ). Under basal conditions, Bk2r Ϫ/Ϫ mice showed higher systolic blood pressure (tail-cuff plethysmography) than wild-type Bk2r ϩ/ϩ and heterozygous Bk2r ϩ/Ϫ mice (121Ϯ2 versus 114Ϯ2 and 115Ϯ2 mm Hg, respectively; PϽ0.05 for both comparisons). Heart rate was higher in Bk2r Ϫ/Ϫ and Bk2r ϩ/Ϫ than in Bk2r ϩ/ϩ (459Ϯ12 and 418Ϯ7 versus 390Ϯ7 bpm; PϽ0.05 for both comparisons). Systolic blood pressure was increased by DOC in transgenic as well as in wild-type mice, whereas no change was induced by the vehicle. The pressor response to DOC was more rapid and pronounced in Bk2r Ϫ/Ϫ than in Bk2r ϩ/ϩ and Bk2r ϩ/Ϫ (30Ϯ5 versus 15Ϯ4 and 6Ϯ3 mm Hg, respectively, at 3 weeks; PϽ0.01 for both comparisons). The difference in systolic blood pressure was consistent with that detected by direct intra-arterial measurements of mean blood pressure. Neither DOC nor its vehicle altered heart rate or gain in body weight over time. Under basal conditions, urinary sodium excretion did not differ between strains. During DOC administration, cumulative urinary sodium excretion was lower in Bk2r Ϫ/Ϫ than in Bk2r ϩ/ϩ (2.59Ϯ0.15 versus 3.31Ϯ0.22 mmol, respectively, during the first week; PϽ0.05). Urinary kinin excretion was increased by DOC in both Bk2r Ϫ/Ϫ (from 0.65Ϯ0.17 to 4.27Ϯ0.80 pmol/24 h; PϽ0.01) and Bk2r ϩ/ϩ (from 0.55Ϯ0.09 to 6.27Ϯ1.48 pmol/24 h; PϽ0.05). The increase in urinary kinin excretion was similar between strains. These results show that integrity of the bradykinin B 2 receptor is essential for regulation of blood pressure and heart rate under basal conditions. In addition, they indicate that activation of the kallikrein-kinin system represents a compensatory response against the development of hypertension induced by mineralocorticoid excess. (Hypertension. 1998;31:1278-1283.) Key Words: mineralocorticoids Ⅲ blood pressure Ⅲ kallikrein-kinin system K inins, the enzymatic products of kininogen cleavage by kallikrein, induce vasodilatation, diuresis, and natriuresis by promoting the release of endothelium-derived relaxing factors and prostaglandins.1-4 They act as local hormones by activating specific receptors named B 1 and B 2 , with most of the cardiovascular and renal effects being mediated by the B 2 receptor.5 It has been hypothesized that a dysfunction of the KKS, leading to unbalanced predominance of vasoconstrictor and antinatriuretic systems, may contribute to the pathogenesis of arterial hypertension. Interestingly, at variance with other models of genetic or experimental hypertension characterized by a defective renal synthesis...

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Mechanism of natriuretic action of bradykinin

Cited by 111 publications

References 0 publications

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

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

Effects of Hoe 140, a bradykinin B₂‐receptor antagonist, on renal function in conscious normotensive rats

Enhanced Blood Pressure Sensitivity to Deoxycorticosterone in Mice With Disruption of Bradykinin B ₂ Receptor Gene

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Mechanism of natriuretic action of bradykinin

Cited by 111 publications

References 0 publications

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

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

Effects of Hoe 140, a bradykinin B2‐receptor antagonist, on renal function in conscious normotensive rats

Enhanced Blood Pressure Sensitivity to Deoxycorticosterone in Mice With Disruption of Bradykinin B 2 Receptor Gene

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Effects of Hoe 140, a bradykinin B₂‐receptor antagonist, on renal function in conscious normotensive rats

Enhanced Blood Pressure Sensitivity to Deoxycorticosterone in Mice With Disruption of Bradykinin B ₂ Receptor Gene