Interaction of bradykinin and angiotensin in the regulation of blood pressure in conscious rats

Buuse, Maarten van den; Kerkhoff, J.F.J. van de

doi:10.1016/0306-3623(91)90092-k

Cited by 5 publications

(3 citation statements)

References 18 publications

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“…Indeed, the magnitudes (30-40 mmHg) of these depressor responses were similar to the magnitude of the depressor effect observed by Genden & Molineaux (1991). Ours is not a particularly novel finding, since bradykinin pretreatment has been previously shown to potentiate the hypotensive effects of ACE inhibition in conscious rats (Van Den Buuse & Kerkhoff, 1991). It does, however, reinforce the point that the response to ACE inhibition is dependent upon the prevailing haemodynamic circumstances, not the least of which is probably the level of plasma renin activity.…”

Section: Inhibition Of Ace By Cfp In Vitro Cfp Displaced [125ii-supporting

confidence: 55%

Role of angiotensin converting enzyme in the vascular effects of an endopeptidase 24.15 inhibitor

Telford

Smith

Lew

et al. 1995

British J Pharmacology

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1 We investigated the role of angiotensin converting enzyme (ACE) in the cardiovascular effects of N-[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Tyr-p-aminobenzoate (cFP), a peptidase inhibitor selective for metalloendopeptidase (EP) E.C. 3.4.24.15. 2 In conscious rabbits, cFP (5 mg kg-', i.v.) markedly slowed the degradation of [3H]-bradykinin, potentiated the depressor response to right atrial administration of bradykinin (10-1000 ng kg-' ), and inhibited the pressor response to right atrial angiotensin I (10-100 ng kg-1 ). In each of these respects, the effects of cFP were indistinguishable from those of the ACE inhibitor, captopril (0.5 mg plus 10 mg kg-'h -1 i.v.). Furthermore, the effects of combined administration of cFP and captopril were indistinguishable from those of captopril alone. 3 In experimentally naive anaesthetized rats, cFP administration (9.3 mg kg-', i.v.) was followed by a moderate but sustained fall in arterial pressure of 13 mmHg. However, in rats pretreated with bradykinin (50 jig kg-') a more pronounced fall of 30 mmHg was observed. Captopril (5 mg kg-') had similar hypotensive effects to those of cFP, and cFP had no effect when it was administered after captopril. 4 CFP displaced the binding of ['25I]-351A (the p-hydroxybenzamidine derivative of lisinopril) from preparations of rat plasma ACE and solubilized lung membrane ACE (KD= 1.2 and 0.14 p M respectively), and inhibited rat plasma ACE activity (K1 = 2.4 jM). Addition of phosphoramidon (10 jLM), an inhibitor of a range of metalloendopeptidases, including neutral endopeptidase (E.C.3.4.24.11), markedly reduced the potency of cFP in these systems. 5 Taken together these findings suggest that the actions of cFP in vivo are attributable to inhibition of ACE rather than EP 24.15. Given that cFP is a poor inhibitor of ACE in the presence of phosphoramidon in vitro, it is likely that cFP is cleaved by a phosphoramidon-sensitive metallopeptidase in vivo to liberate N-[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Ala, a potent ACE inhibitor.

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Section: Inhibition Of Ace By Cfp In Vitro Cfp Displaced [125ii-supporting

confidence: 55%

Role of angiotensin converting enzyme in the vascular effects of an endopeptidase 24.15 inhibitor

Telford

Smith

Lew

et al. 1995

British J Pharmacology

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“…One cannot exclude, however, the possibility that kinins might control vascular resistance and blood flow in specific vascular territories or interact with other vasoregulatory mechanisms such as the renin-angiotensin system (Van Den Buuse & Kerkhoff, 1991).…”

Section: Discussionmentioning

confidence: 99%

Mediation by B₁ and B₂ receptors of vasodepressor responses to intravenously administered kinins in anaesthetized dogs

Nakhostine

Ribuot

Lamontagne

et al. 1993

British J Pharmacology

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1 Vasodepressor responses to intravenous (i.v.) injection of bradykinin (BK) and des-Arg9-BK, a selective B, kinin receptor agonist, were characterized following i.v. pretreatment with selective B, ([Leu8]-des-Arg9-BK) and B2 (Hoe 140) kinin receptor antagonists in anaesthetized dogs. 2 Des-Arg9-BK (0.05-3.3 nmol kg-') produced dose-dependent decreases in mean arterial blood pressure with a ED_0 0.4 nmol kg-'. The vasodepressor effects evoked by des-Arg9-BK (0.6 nmol kg-') and BK (0.2 nmol kg-') were greater after i.v. and i.a. injections, respectively. 3 The vasodepressor response to BK (0.6 nmol kg-') but not to des-Arg9-BK (0.6 nmol kg-') was significantly (P<0.001) blocked by pretreatment with the B2 receptor antagonist, Hoe 140. 4 The vasodepressor response to des-Arg9-BK (0.6 nmol kg-') but not to BK (0.6 nmol kg-') was significantly (P<0.001) reduced by pretreatment with the selective B, receptor antagonist, [Leu8]-desArg9-BK. Although both B, and B2 receptor antagonists caused a transient fall in blood pressure, their inhibitory action was unlikely to be related to a desensitization mechanism. 5 Inhibition of prostaglandin synthesis with indomethacin prevented the vasodepressor response induced by arachidonic acid (1 mg kg-', i.v.) but not that to BK or des-Arg9-BK (0.6 nmol kg-').6 These results suggest, firstly, that the vasodepressor responses to i.v. BK and des-Arg9-BK are mediated by the activation of B2 and B, receptors, respectively; secondly, that prostaglandins are not involved in the vasodepressor responses to kinins. These findings provide pharmacological evidence for the existence of functionally active B, receptors in canine cardiovascular homeostasis.

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“…We have shown in a separate study that medullary-infused 14 C-labeled clentiazem was predominantly concentrated within the medulla and did not diffuse beyond the outer medulla. 13 It has also been observed that intravenously delivered captopril reduces the pressure in the vasa recta capillaries, suggesting that the outflow resistance (the venous resistance) was probably reduced.…”

Section: Selective Alterations Of Renal Medullary Hemodynamicsmentioning

confidence: 99%

Renal medullary captopril delivery lowers blood pressure in spontaneously hypertensive rats.

Mattson

Cowley

1994

Hypertension

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We examined the contribution of renal medullary function to the maintenance of hypertension in spontaneously hypertensive rats by infusing captopril chronically into the renal medullary interstitial space of uninephrectomized rats. Changes in cortical and medullary blood flow were determined using a newly developed optical fiber implantation technique for laser-Doppler flowmetry. Renal medullary interstitial infusion of captopril (5 mg/kg per day) selectively increased medullary blood flow by 40% without altering renal cortical blood flow throughout the 5 days of captopril delivery. In association with the selective increase of medullary perfusion, a significant natriuresis was observed on the second day of the drug infusion, and urine osmolality was significantly reduced during the first 3 days of captopril infusion. Mean arterial I t is well recognized that the kidney plays a fundamental role in the long-term regulation of arterial pressure and that renal abnormalities can contribute importantly to the development and maintenance of hypertension. We and others have shown that kidneys of spontaneously hypertensive rats (SHR) require a greater arterial pressure than kidneys of normotensive WistarKyoto rats to excrete a given amount of sodium and water. 1 -4 Despite the fact that global renal function appears normal at the early stage of hypertension, this abnormality in the acute pressure-natriuresis response of SHR was shown to be associated with a reduced papillary blood flow and renal interstitial fluid pressure. 35 Blunted relationships between papillary blood flow and renal perfusion pressure were clearly shown even in 3-to 4-week-old SHR compared with age-matched WistarKyoto rats. 4 The reduced renal medullary blood flow is the most apparent renal hemodynamic abnormality during the development of hypertension in SHR, because total renal blood flow, cortical blood flow, and glomerular filtration rate have been found to be similar in very young and adult SHR and Wistar-Kyoto rats. 34 We have hypothesized that the reduced medullary blood flow could contribute to the hemodynamic resetting of the pressure-natriuretic relationship and the development of hypertension in SHR.6 ' 7 In the present study we have tested this concept by selectively increasing renal medullary perfusion Received September 8, 1993; accepted in revised form November 29, 1993. From the Department of Physiology, Medical College of Wisconsin, Milwaukee.Correspondence to Allen W. Cowley, Jr, Department of Physiology, Medical College of Wisconsin, Watertown Plank Rd, Milwaukee, WI 53226. pressure was significantly decreased by 20 mm Hg during 5 days of captopril infusion, and the chronic renal function curve was shifted to a lower level of arterial pressure compared with the control values when 0.9% sodium chloride saline vehicle was infused. Intravenously infused captropril at 5 mg/kg per day did not alter mean arterial pressure, excluding the possibility that the hypotensive effect of medullary captopril infusion was due to recir...

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Interaction of bradykinin and angiotensin in the regulation of blood pressure in conscious rats

Cited by 5 publications

References 18 publications

Role of angiotensin converting enzyme in the vascular effects of an endopeptidase 24.15 inhibitor

Role of angiotensin converting enzyme in the vascular effects of an endopeptidase 24.15 inhibitor

Mediation by B₁ and B₂ receptors of vasodepressor responses to intravenously administered kinins in anaesthetized dogs

Renal medullary captopril delivery lowers blood pressure in spontaneously hypertensive rats.

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Interaction of bradykinin and angiotensin in the regulation of blood pressure in conscious rats

Cited by 5 publications

References 18 publications

Role of angiotensin converting enzyme in the vascular effects of an endopeptidase 24.15 inhibitor

Role of angiotensin converting enzyme in the vascular effects of an endopeptidase 24.15 inhibitor

Mediation by B1 and B2 receptors of vasodepressor responses to intravenously administered kinins in anaesthetized dogs

Renal medullary captopril delivery lowers blood pressure in spontaneously hypertensive rats.

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Mediation by B₁ and B₂ receptors of vasodepressor responses to intravenously administered kinins in anaesthetized dogs