Role of angiotensin II and bradykinin on aortic collagen following converting enzyme inhibition in spontaneously hypertensive rats.
We previously showed that chronic angiotensin-converting enzyme (ACE) inhibition prevented the increase in aortic collagen in spontaneously hypertensive rats (SHRs) independently of blood pressure reduction. The aim of the present study was to determine whether the effects of ACE inhibition on aortic fibrosis were due to inhibition of angiotensin II formation, preservation of bradykinin, or a combination of both. Four week-old SHRs were treated for 4 months with the ACE inhibitor quinapril, quinapril with the bradykinin B2 receptor antagonist Hoe 140, or the angiotensin II AT1 receptor antagonist CI996. Control SHR and Wistar-Kyoto (WKY) rats received a placebo for the same period of time. At the end of the treatment, as compared to conscious SHR and WKY controls, quinapril completely prevented the development of hypertension, whereas quinapril-Hoe 140 and the AT1 receptor antagonist produced only a partial reduction of blood pressure. In relation with blood pressure changes, aortic hypertrophy was significantly prevented by quinapril but not by quinapril-Hoe 140 or CI996. In contrast, aortic collagen accumulation was completely prevented by all three treatments. The study provides evidence that in young live SHRs, the prevention of aortic collagen accumulation is independent of blood pressure changes and bradykinin preservation and involves exclusively angiotensin II inhibition through AT1 receptors.
Benetos
A
A
Unit 337, INSERM, Paris, France.
Levy
B I
BI
Lacolley
P
P
Taillard
F
F
Duriez
M
M
Safar
M E
ME
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D065168:Bradykinin Receptor Antagonists; D003094:Collagen / Q000378:metabolism*; D004359:Drug Therapy, Combination; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D006984:Hypertrophy; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007546:Isoquinolines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D000077583:Quinapril; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D043782:Receptor, Bradykinin B2; D044005:Tetrahydroisoquinolines; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D065168:Bradykinin Receptor Antagonists; C092503:CI 996; D007093:Imidazoles; D007546:Isoquinolines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D043782:Receptor, Bradykinin B2; D044005:Tetrahydroisoquinolines; D013777:Tetrazoles; D000804:Angiotensin II; C065679:icatibant; D003094:Collagen; D000077583:Quinapril; D001920:Bradykinin