Angiotensin II generation in the rat vena cava: stimulation of local synthesis by beta-adrenoceptor activation.
There is considerable evidence to suggest that isolated tissues have the capacity to generate angiotensin II and that angiotensin II thus generated may enhance noradrenergic neurotransmission. In the present study the possibility that there may be local formation of angiotensin II within the rat vena cava and its consequence to noradrenergic transmission has been investigated. The angiotensin II precursors, angiotensin I and a synthetic tetradecapeptide renin substrate, each enhanced the stimulation-induced efflux of radioactivity from tissues previously incubated with 3H-noradrenaline. The effects of angiotensin I were blocked by the converting enzyme inhibitor captopril and the receptor antagonist saralasin, indicating local conversion to angiotensin II. The effect of the tetradecapeptide was blocked by saralasin, but not by captopril, suggesting either a direct effect of this peptide or conversion to angiotensin II by a pathway not involving angiotensin converting enzyme. The beta-adrenoceptor agonist isoprenaline enhanced noradrenergic transmission in the rat vena cava, relaxed guinea-pig trachea precontracted with carbachol and increased heart rate in rat isolated atria. Captopril and saralasin blocked the effect of isoprenaline in the vena cava, but did not alter its effects in the atria or trachea. This suggests that in the rat vena cava the facilitation of noradrenergic transmission by isoprenaline may involve stimulation of local angiotensin II production.
Ziogas
J
J
Department of Pharmacology, University of Melbourne, Victoria, Australia.
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D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000096:biosynthesis*; D000808:Angiotensinogen / Q000494:pharmacology; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects / Q000648:ultrastructure; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology; D012504:Saralasin / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000502:physiology; D014316:Tritium; D014683:Vena Cava, Superior / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure
D011943:Receptors, Adrenergic, beta; D014316:Tritium; D000808:Angiotensinogen; D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril; D012504:Saralasin; D007545:Isoproterenol; D009638:Norepinephrine