The actions of bradykinin and lys-bradykinin on tracheal blood flow and smooth muscle in anaesthetized sheep

Corfield, Douglas R.; Webber, Stephanie; Hanafi, Z.; Widdicombe, J. G.

doi:10.1016/0952-0600(91)90057-a

Cited by 15 publications

(6 citation statements)

References 17 publications

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“…Regarding the coronaries, our dynamic experiments show that local resistance is de- Ϫ/Ϫ mice. A potential role for bradykinin in the regulation of coronary resistance and/or blood flow has previously been hypothesized, [31][32][33][34] but to our knowledge, the present study is the first to document in vivo the consequences of a constitutive deficiency of the B 2 receptor in this vascular bed. As expected, dipyridamole infusion elicits no renal vasodilatation in B 2 Ϫ/Ϫ and WT mice, thus confirming the selectivity of this vasodilator agent for the coronary vasculature.…”

Section: Discussionmentioning

confidence: 75%

Cardiovascular Phenotypes of Kinin B ₂ Receptor– and Tissue Kallikrein–Deficient Mice

et al. 2002

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Abstract-To clarify the role of the kallikrein-kinin system in cardiovascular homeostasis, the systemic and regional hemodynamics of kinin B 2 receptor-deficient (B 2 Ϫ/Ϫ ) and tissue kallikrein-deficient (TK Ϫ/Ϫ ) mice were compared with their wild-type (WT) littermates on a pure C57BL/6 genetic background. B 2 Ϫ/Ϫ , TK Ϫ/Ϫ , and WT adult mice were normotensive and displayed normal hemodynamic (left ventricular [LV] pressure, cardiac output, total peripheral resistance, dP/dt max ) and echocardiographic (septum and LV posterior wall thickness, LV diameter, LV mass, and LV fractional shortening) parameters. However, heart rate was lower in B 2 Ϫ/Ϫ mice compared with TK Ϫ/Ϫ and WT mice. In addition, B 2 Ϫ/Ϫ mice, but not TK Ϫ/Ϫ mice, exhibited lower coronary and renal blood flows and greater corresponding vascular resistances than did WT mice, indicating a tonic physiological vasodilating effect of bradykinin in these vascular beds. However, maximal coronary vasodilatation capacity, estimated after dipyridamole infusion, was similar in the 3 groups of mice. B 2 Ϫ/Ϫ mice were significantly more sensitive than were TK Ϫ/Ϫ mice to the vasoconstrictor effects of angiotensin II and norepinephrine. Finally, renin mRNA levels were significantly greater in B 2 Ϫ/Ϫ mice and smaller in TK Ϫ/Ϫ mice compared with WT mice. Taken together, these results indicate that under basal conditions, the kinin B 2 receptor is not an important determinant of blood pressure in mice but is involved in the control of regional vascular tone in the coronaries and the kidneys. The phenotypic differences observed between TK Ϫ/Ϫ and B 2 Ϫ/Ϫ mice could be underlain by tissue kallikrein kinin-independent effect and/or kinin B 1 receptor activation. Key Words: kallikrein-kinin system Ⅲ renin-angiotensin system Ⅲ blood pressure Ⅲ cardiac function Ⅲ blood flow Ⅲ mice K inins are generated from enzymatic cleavage of circulating kininogens by serine proteases such as tissue kallikrein and exert their biological effects through activation of G protein-coupled B 1 and B 2 receptors. 1 In particular, the B 2 receptor is constitutively expressed in the vascular endothelium and mediates the vasodilator effects of kinins. 2 Its role in cardiovascular homeostasis has recently been assessed by the use of B 2 receptor-deficient (B 2 Ϫ/Ϫ ) mice, but there are significant discrepancies in the literature regarding the phenotype of these mice. Thus, the lack of B 2 receptor has been reported to induce either permanent 3-5 or transient hypertension, 6 to induce no hypertension unless the mice are fed a high-salt diet, 7,8 or to never induce hypertension, even on high salt intake. 9 These discrepancies may be explained in part by differences in the genetic background of B 2 Ϫ/Ϫ mice, which was 129Sv, 129SvEvTac, or C57BL/6. More problematic, they could also result from the fact that control mice were not littermates but mice issued from separate strains chosen to match the genetic background of B 2 Ϫ/Ϫ mice. It is known that in these conditions, a genetic shift in m...

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Section: Discussionmentioning

confidence: 75%

Cardiovascular Phenotypes of Kinin B ₂ Receptor– and Tissue Kallikrein–Deficient Mice

et al. 2002

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“…Of these, indomethacin, the cyclo-oxygenase inhibitor, was the only agent to alter baseline conditions and this action is therefore, perhaps, harder to interpret. However, the percentage fall in vascular resistance produced with methacholine is the same before and after indomethacin when there are similar changes in baseline conditions (Corfield et al, 1991). Therefore it appears that indomethacin does not affect the PAF-induced vasodilatation.…”

Section: Discussionmentioning

confidence: 80%

“…These include histamine, methacholine, 5-HT, peptides and prostaglandins (Laitinen et al, 1987;Salonen et al, 1988;Corfield et al, 1991). Here PAF has been shown to be one of the most potent vasodilators yet studied in this system, second only to the other inflammatory mediator bradykinin which is also notable for its extremely long duration of action (Corfield et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of platelet activating factor‐induced changes in sheep tracheal blood flow

Corfield

Webber

Widdicombe

1991

British J Pharmacology

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1 The effects of platelet activating factor (PAF) have been studied on the cervical tracheal vasculature and smooth muscle of anaesthetized sheep. 2 The predominant action of PAF (2 pmol-2 nmol) was a dose-dependent fall in tracheal vascular resistance. The maximum fall in resistance was -41.6% (-38.5 to -44.7%, 95% confidence interval) and the ED50 was 17 pmol (12-28 pmol). Lyso-PAF (200 pmol) did not change vascular resistance.3 PAF had no effect on tracheal smooth muscle tone assessed by measuring changes in the external diameter of the trachea. 4 The fall in vascular resistance produced with PAF was unaffected by the anti-asthma drug nedocromil sodium (1 mg, i.a.), the cyclo-oxygenase inhibitor indomethacin (5mg kg-, i.v.), the leukotriene receptor antagonist FPL55712 (2mgkg-1, i.v.), or a combination of the histamine H1-and H2-antagonists mepyramine (2 mg kg-1, i.v.) with cimetidine (5 mg kg-1, i.v.). The PAF antagonist WEB 2086 (300,ug kg-1, i.v.) significantly reduced the vasodilatation produced by PAF (before, -40.8 + 4.2%; after -16.5 + 5.9%, P <0.05). 5 Thus in this model, PAF is a potent vasodilator of the tracheal circulation but has no action on tracheal smooth muscle. The vasodilatation is mediated by specific PAF receptors and is not due to the release of prostanoids, leukotrienes or histamine.

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“…Bradykinin, which is a powerful vasodilator, increases permeability of bronchial venules when administered into the bronchial circulation (Fishman & Pietra, 1976; Corfield et al 1991). This effect is mediated by B2 receptors (Mashito et al 1999).…”

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confidence: 99%

The rapidly adapting receptors in mammalian airways and their responses to changes in extravascular fluid volume

Kappagoda

Ravindran

2006

Experimental Physiology

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In this short review, we shall focus on some recent findings on the physiological stimulus for the rapidly adapting receptors (RAR) of the airways. They are readily activated by a sustained inflation of the lungs and they are usually identified by their rapid adaptation to this stimulus. They are also activated by both tactile stimuli and irritant gases applied to the epithelium of the airways. The investigations reviewed here suggest that these receptors are activated by changes in extravascular fluid volume. The principal factors governing fluid flux from the microcirculation are identified in the Starling equation. These are the hydrostatic pressure, plasma oncotic pressure and capillary permeability. Findings from recent studies suggest that all these factors increase the activity of RAR. In addition, these receptors are also activated by obstruction of lymph drainage from the lung. Evidence is presented to show that manipulation of Starling forces also increases the extravascular fluid volume of the airways in areas where the RAR are located. On the basis of these findings, it is suggested that, along with mechanosensitivity to stimuli such as stretch, inflation and deflation, another physiological stimulus to the RAR is a change in extravascular fluid volume in the regions of the airways where these receptors are located.

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The actions of bradykinin and lys-bradykinin on tracheal blood flow and smooth muscle in anaesthetized sheep

Cited by 15 publications

References 17 publications

Cardiovascular Phenotypes of Kinin B ₂ Receptor– and Tissue Kallikrein–Deficient Mice

Cardiovascular Phenotypes of Kinin B ₂ Receptor– and Tissue Kallikrein–Deficient Mice

Mechanisms of platelet activating factor‐induced changes in sheep tracheal blood flow

The rapidly adapting receptors in mammalian airways and their responses to changes in extravascular fluid volume

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The actions of bradykinin and lys-bradykinin on tracheal blood flow and smooth muscle in anaesthetized sheep

Cited by 15 publications

References 17 publications

Cardiovascular Phenotypes of Kinin B 2 Receptor– and Tissue Kallikrein–Deficient Mice

Cardiovascular Phenotypes of Kinin B 2 Receptor– and Tissue Kallikrein–Deficient Mice

Mechanisms of platelet activating factor‐induced changes in sheep tracheal blood flow

The rapidly adapting receptors in mammalian airways and their responses to changes in extravascular fluid volume

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Product

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Cardiovascular Phenotypes of Kinin B ₂ Receptor– and Tissue Kallikrein–Deficient Mice

Cardiovascular Phenotypes of Kinin B ₂ Receptor– and Tissue Kallikrein–Deficient Mice