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.
Heart and Stroke/Richard Lewar Centre of Excellence, University of Toronto, Toronto, ON, Canada.
Peter C
PC
Papageorgiou
Erik L
EL
Yeo
Peter H
PH
Backx
John S
JS
Floras
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001681:Biological Assay; D001777:Blood Coagulation; D001794:Blood Pressure; D002216:Captopril / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism; D005174:Factor XII / Q000737:chemistry*; D006339:Heart Rate; D006439:Hemodynamics; D006801:Humans; D007249:Inflammation; D008297:Male; D051381:Rats; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*
D000959:Antihypertensive Agents; D002395:Catecholamines; D005174:Factor XII; D002216:Captopril