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

Abstract

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.

Catharanthine Dilates Small Mesenteric Arteries and Decreases Heart Rate and Cardiac Contractility by Inhibition of Voltage-Operated Calcium Channels on Vascular Smooth Muscle Cells and Cardiomyocytes

“…Detailed methodology for the measurements of BP, HR, dP/dt max , and left ventricular blood pressure performed in rats that were anesthetized with isoflurane was as previously described (Jadhav et al, 2012;Papageorgiou et al, 2012). Either catharanthine (0.5-20 mg/kg) or saline (vehicle) was administered (in volumes ,0.3 ml/kg) via a catheter inserted in the femoral vein.…”

“…On the basis of these findings, further studies conducted at the University of Toronto determined the changes in intracardiac pressures [left ventricular systolic blood pressure (LVSBP)] and cardiac contractility (dP/dt max ) by advancing pressure-volume catheter (SPR-838; Millar Instruments, Houston, TX) through a cannula inserted into the right common carotid artery into the left ventricle. From the data gathered, it was feasible to calculate the changes in left ventricular volume and the slope of the end-systolic pressure-volume relationship (ESPVR) curves before and after the administration of catharanthine at 1, 3, and 10 mg/kg (Papageorgiou et al, 2012).…”

Coagulation Factor XIIa-kinin-mediated contribution to hypertension of chronic kidney disease

“…The catheter was then advanced into the left ventricle and baseline intracavity pressure and left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume were recorded in triplicate. From these values SV, CO and TPR were derived, as previously described [9]. Subsequently, blood ($500 ml) was collected for FXIIa analysis using a rat ELISA without cross-reactivity with FXII zymogen or FXIIa:inhibitor complexes [24].…”

“…Importantly, these acute catecholamine and haemodynamic responses are absent both in adrenal-medullectomized Brown Norway rats and in the Brown Norway Katholiek (BNK) strain [7] (which carries a spontaneous single point gene mutation that impairs hepatic secretion of kininogen [8]), establishing that both an intact plasma KKS and adrenal glands are required to elicit these immediate effects. In neurally intact, lightly anaesthetized Brown Norway rats, a 60-min infusion of FXIIa increases its plasma concentration three-fold and causes adrenal catecholaminemediated increases in both peripheral resistance and BP that persist beyond its cessation [9].…”