Effect of angiotensin converting enzyme inhibitors on cardiac noradrenaline release.
Angiotensin II facilitates sympathetic transmitter release in the heart. Thus, angiotensin converting enzyme inhibitors may be assumed to suppress noradrenaline release in the heart. To test this hypothesis endogenous noradrenaline release was induced either by electrical stimulation of the stellate ganglion or by global ischaemia in rat hearts. Noradrenaline was determined by high performance liquid chromatography in coronary venous overflow. Endogenous angiotensin formation was blocked by the angiotensin converting enzyme inhibitors captopril and ramiprilat and the activity of the endogenous renin-angiotensin system was modulated by variations in nutritional sodium load prior to the experiments. Both angiotensin converting enzyme inhibitors significantly reduced noradrenaline release evoked by nerve stimulation when the animals had been fed a low sodium diet. Following a high sodium diet, however, captopril and ramiprilat had no effect on stimulation-induced noradrenaline release. Global ischaemia (20 min) resulted in noradrenaline overflow from sympathetic nerves, independent of nerve stimulation. This ischaemia-induced noradrenaline release was not influenced by either converting enzyme inhibitor. In conclusion, the results suggest a sodium-dependent endogenous angiotensin formation in the heart which facilitates physiological noradrenaline release and is sensitive to angiotensin converting enzyme inhibitors. In contrast, noradrenaline release in ischaemia is not affected by converting enzyme blockers, due to a different, non-exocytotic release mechanism of noradrenaline during myocardial ischaemia.
Richardt
G
G
Department of Cardiology, University of Heidelberg, Germany.
Kranzhöfer
R
R
Schömig
A
A
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D003327:Coronary Disease / Q000503:physiopathology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology*; D017257:Ramipril / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D011758:Pyrroles; C052549:ramiprilat; D002216:Captopril; D012964:Sodium; D017257:Ramipril; D009638:Norepinephrine