Angiotensin 1–7 Induces Bradykinin-Mediated Relaxation in Porcine Coronary Artery1
- Hypertension and Vascular Research Division, Heart and Vascular Institute, Henry Ford Hospital, Detroit, Michigan
Abstract
Angiotensin 1–7 (Ang 1–7) has been reported to induce relaxation which is partially blocked by a kinin receptor antagonist. We investigated the relationship between kinins and angiotensin peptides with use of preconstricted isolated pig coronary arteries. Ang 1–7 alone (up to 10−5 M) had no relaxant effect. Bradykinin (BK) (10−10–10−7 M) induced transient relaxation, returning to basal tone, although BK remained in the bath. In these BK-stimulated rings, Ang 1–7 but not BK (both 5 × 10−6 M) again relaxed the rings by approximately 50%. This relaxation was blocked by a BK B2 antagonist, a kininase, and a nitric oxide synthase inhibitor. Ang 1–7 inhibited purified angiotensin-converting enzyme (ACE) by 30 ± 3.5% (n = 4) at 10−6 M. However, in BK-pretreated rings, the ACE inhibitor ramiprilat did not induce relaxation, nor did it affect the relaxant response to Ang 1–7, which suggests that the effect of Ang 1–7 was not caused by ACE inhibition. Ang 1–7-induced vasodilation was reduced by 69.9 ± 6.2% by an AT2receptor blocker, PD-123319, and 29.3 ± 7.3% by an AT1 antagonist, losartan. Neither the nonselective AT1/AT2 receptor antagonist sarthran nor saralasin inhibited the response to Ang 1–7. Ang II did not elicit relaxation either alone or in the presence of losartan, which suggests that activation of AT2 receptors does not cause relaxation. Thus, in the presence of bradykinin, Ang 1–7 relaxes pig coronary arteries via a PD-123319-sensitive mechanism involving nitric oxide, kinins and the BK B2 receptor. The kallikrein-kinin and renin-angiotensin systems may be linked through the interaction of Ang 1–7 and BK.
Footnotes
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Send reprint requests to: A. Guillermo Scicli, Ph.D., Eye Care Services Research, Henry Ford Hospital, One Ford Place, 4D, Detroit, MI 48202-3450.
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↵1 This research was supported in part by grant 15-PO1-HL-28982 from the National Heart, Lung and Blood Institute of the National Institutes of Health.
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↵2 Present address: Eye Care Services Research, Henry Ford Hospital, One Ford Place, 4D; Detroit, MI 48202-3450.
- Abbreviations:
- Ang 1–7
- angiotensin 1–7
- ACE
- angiotensin-converting enzyme
- ACEi
- angiotensin-converting enzyme inhibitor
- l-NAME
- NG-nitro-l-arginine methyl ester
- EDHF
- endothelium-derived hyperpolarizing factor
- NO
- nitric oxide
- NOS
- NO synthase
- PGF
- prostaglandin F
- U46619
- 9,11-dideoxy-11a,9a-epoxy-methano-PGF2a
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- Received July 22, 1997.
- Accepted March 20, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
