Interaction of bradykinin and angiotensin in the regulation of blood pressure in conscious rats.
1. The interaction between bradykinin (BK) and the renin-angiotensin system was studied in conscious, catheterized rats. 2. Intravenous injection of BK induced dose-dependent decreases in blood pressure in normotensive Wistar and Wistar-Kyoto rats and spontaneously hypertensive rats. Pretreatment with the angiotensin-converting enzyme (ACE) inhibitor captopril markedly enhanced the effect of BK, such that the dose-response curve shifted significantly to the left in all three strains. 3. In a second series of experiments, captopril did not change basal blood pressure, but blocked the pressor response to angiotensin I (AI), but not angiotensin II (AII). 4. The partial agonist Sar1-Ala8-angiotensin II (SAR) increased blood pressure and blocked the pressor response to subsequent AII treatment. 5. After pretreatment with BK (50 micrograms/kg), captopril evoked a decrease in blood pressure, while still blocking the effect of AI. 6. After pretreatment with BK, SAR decreased blood pressure, while still antagonizing the action of AII. 7. These results suggest that ACE plays a role in the inactivation of circulating BK in normotensive and hypertensive rats. Conversely, BK can influence the activity of the renin-angiotensin system, probably by interacting with ACE.
Rudolf Magnus Institute for Pharmacology, University of Utrecht, The Netherlands.
M
M
van den Buuse
J
J
Kerkhoff
D000110:Acetylcholinesterase / Q000378:metabolism; D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000008:administration & dosage*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000008:administration & dosage*; D002216:Captopril / Q000494:pharmacology; D004347:Drug Interactions; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012084:Renin-Angiotensin System / Q000187:drug effects; D012504:Saralasin / Q000494:pharmacology
D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril; D000110:Acetylcholinesterase; D012504:Saralasin; D001920:Bradykinin