Activated plasma coagulation β-Factor XII-induced vasoconstriction in rats

By inducing BK (bradykinin)-stimulated adrenomedullary catecholamine release, bolus injection of the β-fragment of activated plasma coagulation Factor XII (β-FXIIa) transiently elevates BP (blood pressure) and HR (heart rate) of anaesthetized, vagotomized, ganglion-blocked, captopril-treated bioassay rats. We hypothesized that intravenous infusion of β-FXIIa into intact untreated rats would elicit a qualitatively similar vasoconstrictor response. BN (Brown Norway) rats received for 60 min either: (i) saline (control; n=10); (ii) β-FXIIa (85 ng/min per kg of body weight; n=9); or (iii) β-FXIIa after 2ADX (bilateral adrenalectomy; n=9). LV (left ventricular) volume and aortic BP were recorded before (30 min baseline), during (60 min) and after (30 min recovery) the infusion. TPR (total peripheral resistance) was derived from MAP (mean arterial pressure), SV (stroke volume) and HR. Saline had no haemodynamic effects. β-FXIIa infusion increased its plasma concentration 3-fold in both groups. In adrenally intact rats, β-FXIIa infusion increased MAP by 6% (5±2 mmHg) and TPR by 45% (0.50±0.12 mmHg/ml per min), despite falls in SV (−38±8 μl) and HR [−18±5 b.p.m. (beats/min)] (all P<0.05). In 2ADX rats, β-FXIIa had no HR effect, but decreased SV (−89±9 μl) and MAP (−4±1 mmHg), and increased TPR by 66% (0.59±0.15 mmHg/ml per min) (all P<0.05). After infusion, adrenally intact rats exhibited persistent vasoconstriction (MAP, 10±1 mmHg; TPR, 0.55±0.07 mmHg/ml per min; both P<0.05), whereas in 2ADX rats, MAP remained 5±1 mmHg below baseline (P<0.05) and TPR returned to baseline. End-study arterial adrenaline (epinephrine) concentrations in the three groups were 1.9±0.6, 9.8±4.1 and 0.6±0.2 nmol/l respectively. Thus, in neurally intact lightly anaesthetized untreated rats, β-FXIIa infusion induces both adrenal catecholamine-mediated and adrenally independent increases in peripheral resistance

Endothelial kinin B1-receptors are induced by myocardial ischaemia-reperfusion in the rabbit

Kinin B1-receptors are induced by various inflammatory stimuli. Since myocardial ischaemia-reperfusion results in inflammation, we questioned whether it could induce B1-receptor-dependent responses to des-Arg9-bradykinin (DBK).Thirty-six rabbits were submitted either to a 30 min coronary occlusion followed by a 3 h reperfusion or to a sham operation. The response to DBK was then tested in vivo on mean arterial pressure (MAP) and in vitro on isolated hearts and arterial rings.DBK induced a dose-dependent decrease in MAP in the ischaemia-reperfusion group (DBK, 10 μg kg−1, intra-arterial: -12 ± 2 vs. -5 ± 2 mmHg in the sham group, P < 0.02), which was significantly antagonised by [Leu8]-des-Arg9-bradykinin (LBK), a B1-receptor antagonist. Following ischaemia-reperfusion, isolated hearts responded to DBK by a decrease in coronary perfusion pressure greater than that of the sham group. DBK dose-dependently decreased the isometric force of isolated carotid rings (DBK, 10−5m: -9 ± 2 vs. -1 ± 2 % in the sham group, P < 0.02) and mesenteric arteries (DBK, 10−6m: -38 ± 7 %vs. -3 ± 2 % in the sham group, P < 0.001). The vascular effects of DBK seen after ischaemia-reperfusion were significantly antagonised by LBK. The presence of B1-receptors in ischaemia-reperfusion animals was confirmed by immunolocalisation and Western blot analysis.This study demonstrates that myocardial ischaemia-reperfusion induces a global induction of functional kinin B1-receptors in the endothelium

Detrimental implication of B-1 receptors in myocardial ischemia: evidence from pharmacological blockade and gene knockout mice

Objective: the aim of this study was to evaluate the contribution of kinin B-1 receptors in myocardial ischemia using both pharmacological blockade and gene knockout mice. Material and methods: Hearts (n=6-8 per group) from wild type or homozygous B-1 receptor gene knockout mice were isolated and perfused using the Langendorff technique. After a 30-min stabilisation period, the left coronary artery was occluded for 30 min followed by 60 min of reperfusion. in two separate groups of wild type hearts, B-1 and B-2 receptors were blocked with 3 nM of (des-Arg(9), Leu(8))-bradykinin and 10 nM of Hoe 140, respectively, (started 15 min before ischemia and stopped before the reperfusion). Results: Infarct size to risk zone (I/R) ratio was significantly reduced in hearts of knockout mice (11.3 +/- 2.1%) compared to those of wild type mice (25.7 +/- 1.7%). Furthermore, in wild type mice, I/R was significantly reduced in hearts perfused with the B-1 receptor antagonist (12.8 +/- 2.4%) but not in hearts perfused with the B-2 receptor antagonist (36.3 4.4%) compared to untreated hearts. Finally, a RTPCR technique showed an activation of kinin B-1 receptor gene transcription, in wild type hearts, subjected to the ischemia-reperfusion sequence. Conclusion: This study demonstrates that B-1 receptors are induced during myocardial ischemia where they could play a detrimental role in mice. (C) 2002 Published by Elsevier Science B.V.Univ Grenoble 1, Lab Stress Cardiovasc & Pathol Associees, F-38706 La Tronche, FranceMax Delbruck Ctr Mol Med, D-13092 Berlin, GermanyEscola Paulista Med, Dept Biophys, BR-04023062 São Paulo, BrazilEscola Paulista Med, Dept Biophys, BR-04023062 São Paulo, BrazilWeb of Scienc

Structural heterogeneity of the rat pulmonary vein myocardium: consequences on intracellular calcium dynamics and arrhythmogenic potential

Abstract Mechanisms underlying ectopic activity in the pulmonary vein (PV) which triggers paroxysmal atrial fibrillation are unknown. Although several studies have suggested that calcium signalling might be involved in these arrhythmias, little is known about calcium cycling in PV cardiomyocytes (CM). We found that individual PV CM showed a wide range of transverse tubular incidence and organization, going from their virtual absence, as described in atrial CM, to well transversally organised tubular systems, like in ventricular CM. These different types of CM were found in groups scattered throughout the tissue. The variability of the tubular system was associated with cell to cell heterogeneity of calcium channel (Cav1.2) localisation and, thereby, of Cav1.2-Ryanodine receptor coupling. This was responsible for multiple forms of PV CM calcium transient. Spontaneous calcium sparks and waves were not only more abundant in PV CM than in LA CM but also associated with a higher depolarising current. In conclusion, compared with either the atrium or the ventricle, PV myocardium presents marked structural and functional heterogeneity

Delayed myocardial protection induced by endotoxin does not involve kinin B(1)-receptors

1. Endotoxin is known to confer a delayed protection against myocardial infarction. Lipopolysaccharide (LPS) treatment also induces the de novo synthesis of kinin B(1)-receptors that are not present in normal conditions. The aim of this study was to evaluate whether LPS-induced B(1)-receptors are implicated in the reduction of infarct size brought about by LPS. 2. Rabbits were submitted to a 30-min coronary artery occlusion and 3-h reperfusion sequence. Six groups were studied: pretreated or not (control animals) with LPS (5 μg kg(−1) i.v.) 24 h earlier and treated 15 min before and throughout ischaemia–reperfusion with either the B(1)-antagonist R-715 (1 mg kg(−1) h(−1)), the B(1)-agonist Sar-[D-Phe(8)]-des-Arg(9)-bradykinin (15 μg kg(−1) h(−1)) or vehicle (saline). Infarct size and area at risk were assessed by differential staining and planimetric analysis. 3. The presence of B(1)-receptors in LPS-pretreated animals was confirmed by a decrease in mean arterial pressure in response to B(1) stimulation. LPS-pretreatment significantly reduced infarct size (6.4±1.7%, of area at risk vs 24.1±2.5% in control animals, P<0.05). This protection was not modified by B(1)-receptor antagonism (7.4±2.2%, NS) or stimulation (5.2±1.2%, NS). Neither antagonist nor agonist modified infarct size in control animals. 4. In conclusion, these data suggest that LPS-induced myocardial protection in the rabbit is not related to concomitant de novo B(1)-receptor induction