Hemodynamic effects of bradykinin on systemic and pulmonary circulation in healthy and hypertensive humans.
In our studies, we investigated the vasodepressor effects of bradykinin in vivo in normotensive and hypertensive subjects. Bradykinin was injected intravenously and intra-arterially (40-6,050 pM/kg) and was infused intra-arterially (40-6,050 pM/kg/min). The investigations were performed in 21 normotensive and 15 hypertensive patients. Bradykinin injections were performed after the following pharmacological interventions: salt restriction (10 mmol of Na/day), salt loading (300 mmol of Na/day), captopril (50 mg), ramipril (5 mg), lisinopril (20 mg), ketotifen (2 X 1 mg), indomethacin (2 X 50 mg), and propranolol (80 mg). The results show that bradykinin lowers blood pressure in a dose-related manner by marked reduction in peripheral vascular resistance. The blood pressure reduction was strongly correlated with the increase in kinin concentration. This effect of bradykinin appears to be independent of changes in sodium metabolism, beta-adrenoceptors, histamine-1 receptors, and prostaglandins. ACE inhibitors protentiate the blood pressure-lowering effect of bradykinin approximately 20- to 50-fold. In the case of intra-arterial injection of bradykinin, only 2-5% of the intravenously used dose of bradykinin are needed to produce an identical fall in blood pressure. From these experiments, a pulmonary clearance rate of bradykinin of over 95% can be calculated. In the pulmonary arteries, bradykinin has no effect on vascular resistance. In patients suffering from primary or renovascular hypertension, the blood pressure response to bradykinin was enhanced. The bradykinin potentiating effect of the ACE inhibitors was not altered in the hypertensives. In patients suffering from borderline hypertension or primary hyperaldosteronism, bradykinin caused the same blood pressure lowering effect as in the normotensives.
Department of Internal Medicine II, University of Cologne, Merheim Hospital, F.R.G.
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G
Bönner
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Preis
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U
Schunk
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C
Toussaint
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Kaufmann
D000328:Adult; D000803:Angiotensin I / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology; D002302:Cardiac Output / Q000187:drug effects; D004656:Enalapril / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D017706:Lisinopril; D008297:Male; D008875:Middle Aged; D011652:Pulmonary Circulation / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D000803:Angiotensin I; D002216:Captopril; D017706:Lisinopril; D001920:Bradykinin