Kinin receptors in human vascular tissue: their role in atheromatous disease

Raidoo, Deshandra M.; Ramsaroop, Reena; Naidoo, Strinivasen; Müller‐Esterl, Werner; Bhoola, K. D.

doi:10.1016/s0162-3109(97)00015-5

Cited by 80 publications

(52 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…13,14 By use of a specific antibody directed to the peptide sequences of B 1 receptors, it has recently been shown in humans that B 1 receptors are present not only in vascular endothelial and smooth muscle cells of large elastic arteries but also in muscular arteries, such as coronary arteries and muscular arterioles. 15 The notion that B 1 receptors are constitutively expressed in coronary vessels is supported by the present study, which shows the functional coronary effects of des-Arg 9 -bradykinin in the absence of evidence of inflammation by blood analysis. Although bradykinin can be metabolized into des-Arg 9 -bradykinin in dogs, the lack of effects of bradykinin through B 1 receptor stimulation after Hoe 140 pretreatment that we observed may be related to the fact that injected doses of bradykinin were lower than the dose of des-Arg 9 -bradykinin producing any significant effect.…”

Section: Discussionsupporting

confidence: 70%

“…31 In addition, a recent study reports that B 1 receptors are more abundant than B 2 receptors in atheromatous plaques of human coronary vessels, suggesting that B 1 receptors may be involved in atheromatous disease. 15 In conclusion, the present study shows for the first time that under physiological conditions, bradykinin B 1 receptors are functionally present in canine coronary vessels and that their stimulation produces vasodilation in conductance and resistance vessels that is mediated in large part by NO and is not modulated by ACE inhibition. Although the coronary vasodilation induced by B 1 receptor stimulation is less potent than that produced by B 2 receptor stimulation under physiological conditions, the stimulation of B 1 receptors may exert potent vasoactive coronary effects in pathological conditions (such as local or systemic inflammation and sepsis) in which B 1 receptors can be upregulated.…”

Section: Discussionsupporting

confidence: 51%

“…[12][13][14] In humans, a recent in vitro study using immunolabeling techniques revealed the presence of B 1 receptors in vascular endothelial and smooth muscle cells of large elastic arteries, muscular arteries (such as coronary arteries), and muscular arterioles. 15 The functional role of constitutive B 1 receptors in the arterial vessels of dogs is well documented. [12][13][14] The stimulation of these receptors produces a vasorelaxation and a reduction in blood pressure.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Stimulation of Bradykinin B ₁ Receptors Induces Vasodilation in Conductance and Resistance Coronary Vessels in Conscious Dogs

Houël

Héloire

et al. 2000

Circulation

View full text Add to dashboard Cite

Background-Constitutive bradykinin B 1 receptors have been identified in dogs; however, their physiological implications involving the coronary circulation remain to be determined. This study examined, in conscious dogs, the coronary response to des-Arg 9 -bradykinin (a B 1 receptor agonist) and the mechanisms involved. Methods and Results-Eleven dogs were instrumented with a left ventricular micromanometer, a circumflex coronary catheter, a cuff occluder, a Doppler flow probe, and ultrasonic crystals to measure coronary blood flow velocity (CBFv) and coronary diameter (CD). Intracoronary des-Arg 9 -bradykinin (3 to 100 ng/kg) and bradykinin (0.1 to 10 ng/kg) did not modify systemic hemodynamics but dose-dependently increased CBFv and CD. Des-Arg 9 -bradykinin was less potent than bradykinin. Hoe 140 (a B 2 antagonist, 10 g/kg) abolished the effects of bradykinin but did not influence the effects of des-Arg 9 -bradykinin. When CBFv increase was prevented by the cuff occluder, CD responses to bradykinin and des-Arg 9 -bradykinin were maintained. Intracoronary lisinopril (0.75 mg) increased the CD response to bradykinin, with only minimal effect on CBFv, and extended the duration of the effect. Lisinopril did not alter des-Arg 9 -bradykinin responses. Intracoronary N -nitro-L-arginine (2 mg/kg) decreased the CD effect of bradykinin and prevented the CBFv and CD effects of des-Arg 9 -bradykinin. The relaxing effect of des-Arg 9 -bradykinin on isolated coronary rings was prevented by des-Arg 9 ,[Leu 8 ]-bradykinin. Conclusions-In the conscious dog, B 1 receptors are present in coronary vessels, and their stimulation produces vasodilation in conductance and resistance vessels, which is mediated essentially by NO but not modulated by angiotensin-converting enzyme. However, the coronary vasodilation induced by B 1 receptor stimulation is not as great as that produced by B 2 receptor stimulation.

show abstract

Section: Discussionsupporting

confidence: 70%

Section: Discussionsupporting

confidence: 51%

mentioning

confidence: 99%

See 1 more Smart Citation

Stimulation of Bradykinin B ₁ Receptors Induces Vasodilation in Conductance and Resistance Coronary Vessels in Conscious Dogs

Houël

Héloire

et al. 2000

Circulation

View full text Add to dashboard Cite

show abstract

“…This finding suggests that the kinin B 2 receptor exerts a tonic vasodilating effect in these 2 vascular territories, where the presence of B 2 receptors has been described in both endothelial and smooth muscle cells. 30 However, this tonic vasodilating effect does not affect the entire vasculature, as total peripheral resistance is not different between B 2 Ϫ/Ϫ and WT mice. Regarding the coronaries, our dynamic experiments show that local resistance is de- Ϫ/Ϫ mice.…”

Section: Discussionmentioning

confidence: 92%

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

et al. 2002

View full text Add to dashboard Cite

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...

show abstract

“…Apart from their role in the formation of human atherosclerotic plaques (19), the kinin receptors also play an important role in the instability of the plaques in the cardiovascular systems and carotid artery (15,25,26), making them ideal targets for preventing and treating systematic atherosclerosis. Furthermore, it has been demonstrated on experimental models that the blockage of B1R may reduce the systematic inflammatory response and therefore prevent the formation of atherosclerotic plaques (27).…”

Section: Discussionmentioning

confidence: 99%

Expression of the genes encoding kinin receptors are increased in human carotid atherosclerotic plaques

Guo

Liu

et al. 2015

Biomedical Reports

View full text Add to dashboard Cite

Abstract. There is increasing evidence showing that inflammation occurs in atherosclerosis and contributes to the formation of atherosclerotic plaques. As important inflammatory peptides, kinins are increased in inflammation, eliciting vasodilation, increasing vascular permeability and recruiting inflammatory cells to the injury sites by activating specific receptors, B1 and B2. The two receptors have been reported to increase in inflammation, but their expressions remain to be defined in human carotid atherosclerotic plaques (CAP). In order to assess the gene expression of kinin receptors in human CAP, 47 CAP specimens were collected from patients undergoing endarterectomy and classified into stable and unstable plaque groups, respectively, with 10 mesenteric arteries used as controls. Total mRNA of B1R and B2R was extracted from CAPs and their levels were determined using reverse transcription-polymerase chain reaction. The expression of B1R and B2R mRNA was significantly upregulated in human CAPs compared to the control arteries. In the unstable plaques, the ratios of B1R to the β-actin mRNA level were significantly increased relative to the stable plaques. However, no notable differences were observed in the ratios of B2R to β-actin in mRNA expression between the stable and unstable plaques. The present study suggests that kinin-mediated inflammation involves the formation of atherosclerotic plaque and B1R plays an important role in plaque instability, indicating that kinin receptors can be used as potential targets for future therapeutic interventions.

show abstract

Kinin receptors in human vascular tissue: their role in atheromatous disease

Cited by 80 publications

References 25 publications

Stimulation of Bradykinin B ₁ Receptors Induces Vasodilation in Conductance and Resistance Coronary Vessels in Conscious Dogs

Stimulation of Bradykinin B ₁ Receptors Induces Vasodilation in Conductance and Resistance Coronary Vessels in Conscious Dogs

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

Expression of the genes encoding kinin receptors are increased in human carotid atherosclerotic plaques

Contact Info

Product

Resources

About

Kinin receptors in human vascular tissue: their role in atheromatous disease

Cited by 80 publications

References 25 publications

Stimulation of Bradykinin B 1 Receptors Induces Vasodilation in Conductance and Resistance Coronary Vessels in Conscious Dogs

Stimulation of Bradykinin B 1 Receptors Induces Vasodilation in Conductance and Resistance Coronary Vessels in Conscious Dogs

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

Expression of the genes encoding kinin receptors are increased in human carotid atherosclerotic plaques

Contact Info

Product

Resources

About

Stimulation of Bradykinin B ₁ Receptors Induces Vasodilation in Conductance and Resistance Coronary Vessels in Conscious Dogs

Stimulation of Bradykinin B ₁ Receptors Induces Vasodilation in Conductance and Resistance Coronary Vessels in Conscious Dogs

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