Bradykinin B2 receptor gene (???58T/C) polymorphism influences baroreflex sensitivity in never-treated hypertensive patients

Milan, Alberto; Mulatero, Paolo; Williams, Tracy Ann; Carra, Renata; Schiavone, Domenica; Martuzzi, Roberto; Rabbia, Franco; Veglio, Franco

doi:10.1097/00004872-200501000-00014

Cited by 24 publications

(13 citation statements)

References 21 publications

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“…On the other hand, BK acting through B 2 and atypical receptors is involved in central mechanisms of cardiovascular regulation, and its cardioinhibitory effect may be attributed to deregulation of the autonomic control of the heart rhythm. 13,14 In the in vitro uterus assay, compounds III and VII exhibited negligible agonistic properties, while their acylated counterparts IV and VIII were inactive. Peptides I, II, V, and VI showed varying degrees of antagonistic activity ranging from very low antagonism (pA 2 ≈ 5.5) to rather potent antagonism (pA 2 ) 7.4).…”

Section: Resultsmentioning

confidence: 99%

New Bradykinin Analogues Modified in the C-Terminal Part with Sterically Restricted 1-Aminocyclohexane-1-carboxylic Acid

et al. 2005

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In the present work, a sterically constrained noncoded amino acid, 1-aminocyclohexane-1-carboxylic acid (Acc), was substituted in position 8 of the peptide chain of bradykinin (BK) and position 6, 7, or 8 of its B2 receptor antagonist [D-Arg0,Hyp3,Thi,(5,8)D-Phe7]BK, previously synthesized by Stewart's group, to reduce the flexibility of the peptides, thus forcing the peptide backbone and side chains to adopt specific orientations. Knowing that acylation of the N-terminus of several known B2 blockers with a variety of bulky groups has consistently improved their antagonistic potency in the rat blood pressure assay, the Acc substituted analogues were also synthesized in the N-acylated form with 1-adamantaneacetic acid (Aaa). The activity of eight new analogues was assayed in isolated rat uterus and in rat blood pressure tests. The results clearly demonstrated the importance of the position in the peptide chain into which the sterically restricted Acc residue was inserted. Meanwhile, Acc at positions 6 and 7 led to reduction of antagonistic qualities or even restored the agonism, respectively. Acc at position 8 enhanced antagonistic qualities in both tests. The Acc at position 8 of BK strongly reduced the agonistic potency. In most cases acylation of the N-terminus led either to enhancement of antagonistic potencies or to further decrease of agonistic potency. Our findings offer new possibilities for designing new potent and selective B2 blockers.

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Section: Resultsmentioning

confidence: 99%

New Bradykinin Analogues Modified in the C-Terminal Part with Sterically Restricted 1-Aminocyclohexane-1-carboxylic Acid

et al. 2005

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“…It has been well recognized that BRS is impaired in hypertensive humans and animals [22][23][24][25] . Accordingly, we demonstrated that the LH rats had lower BRS than the LL rats.…”

Section: Discussionmentioning

confidence: 99%

The susceptibility of ventricular arrhythmia to aconitine in conscious Lyon hypertensive rats

Wang

Xie

et al. 2007

Acta Pharmacologica Sinica

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Aim: The present work was designed to investigate the relationship between hemodynamic parameters and the susceptibility of ventricular arrhythmia to aconitine in conscious Lyon hypertensive rats (LH). Methods: Male LH and Lyon low blood pressure rats (LL) were used. After the determination of baroreflex sensitivity (BRS), ventricular arrhythmia was induced by aconitine infusion in conscious rats. Blood pressure (BP) was recorded during the period of infusion. Results: Compared with the LL rats, the LH rats possessed significantly higher BP, blood pressure variability and lower BRS. The threshold of aconitine required for ventricular fibrillation and cardiac arrest in the LH rats were significantly lower than those in the LL rats. It was found that all the hemodynamic parameters studied were not correlated with the threshold of aconitine required for arrhythmia, with the exception of BRS, which was positively related to the threshold of aconitine required for ventricular premature beat. Conclusion: The LH rats possessed greater susceptibility to aconitine-induced ventricular arrhythmias when compared to the LL rats. This greater susceptibility could not be attributed to any one of the hemodynamic parameters alone studied in the LH rats. It is proposed that various hypertension-associated abnormalities, including the abnormal hemodynamics, may co-contribute to this vulnerability to ventricular arrhythmias.

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“…Most evidence suggests that BRS is partly influenced by genetic factors [4], and indeed previously identified polymorphisms seem to explain part of the variance in BRS [30,31]. However, until now only one study reported on the heritability of BRS, in that case obtained from 5-min measurements during a rest condition [5].…”

Section: Discussionmentioning

confidence: 99%

Genetic influences on baroreflex sensitivity during rest and mental stress

Riese

Rijsdijk

Ormel

et al. 2006

Journal of Hypertension

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Bradykinin B2 receptor gene (???58T/C) polymorphism influences baroreflex sensitivity in never-treated hypertensive patients

Abstract: B2R genotype can explain part of the BRS variation that is unaccounted for by simple anthropometric variables and common risk factors.

Cited by 24 publications

References 21 publications

New Bradykinin Analogues Modified in the C-Terminal Part with Sterically Restricted 1-Aminocyclohexane-1-carboxylic Acid

New Bradykinin Analogues Modified in the C-Terminal Part with Sterically Restricted 1-Aminocyclohexane-1-carboxylic Acid

The susceptibility of ventricular arrhythmia to aconitine in conscious Lyon hypertensive rats

Genetic influences on baroreflex sensitivity during rest and mental stress

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