Prejunctional effects of angiotensin II and bradykinin in the heart and blood vessels.
1. Angiotensin and bradykinin facilitate the release of noradrenaline from sympathetic nerve terminals and cause positive inotropy in rat isolated atria and ventricles. The effect of bradykinin was enhanced by the ACE inhibitor, ramiprilat. 2. The facilitated release of noradrenaline in rat ventricle by bradykinin was blocked by the beta2-receptor antagonist HOE-140. This response is also reduced by removing the endocardium, suggesting the release of a mediator from the endocardium. 3. The facilitated noradrenaline release by angiotensin II and bradykinin was blocked by the angiotensin receptor antagonist saralasin to the same extent. In contrast, losartan caused only minor blockade in a range of vascular and cardiac tissues. This suggests that angiotensin and bradykinin exert these responses by interacting with a prejunctional receptor different from the established AT1 subtype. 4. These results suggest that bradykinin mediates facilitation of noradrenaline release via the local release of angiotensin onto an atypical AT1 receptor.
Moura
D
D
Institute of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
Pinheiro
H
H
Paiva
M Q
MQ
Guimarães
S
S
D000804:Angiotensin II / Q000494:pharmacology* / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology* / Q000502:physiology; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D001920:Bradykinin; D009638:Norepinephrine