Does converting enzyme inhibition change the neuronal and extraneuronal uptake of catecholamines?
In previous studies concerning the sympathetic outflow during converting enzyme inhibition, no significant changes after chronic treatment could be observed. Therefore, we investigated the effects of the long-acting converting enzyme inhibitor ramipril on the neuronal and extraneuronal uptake of SHR. Ramipril was administered either i.v. or orally to SHR, whereas desipramine or corticosterone were additionally infused to block the neuronal or extraneuronal uptake of catecholamines. As an index of sympathetic outflow, plasma noradrenaline and adrenaline concentrations were determined during preganglionic stimulation of the spinal cord using HPLC and ELCD. Blood pressure of SHR was measured in a carotid artery and was significantly decreased in the ramipril treated group under resting and stimulating conditions. Ramipril did not influence stimulated sympathetic outflow. However, in acute and chronic experiments ramipril led to an additive effect to desipramine concerning stimulated circulating catecholamines. Similar results could be obtained after blocking the uptake-2 with corticosterone. 3H-NA-uptake into the hearts of SHR was significantly diminished by about 10% after chronic ramipril administration. It is suggested that ramipril is able to decrease the neuronal and extraneuronal uptake of catecholamines by an unspecific effect due to the comparably high lipophilicity. The blood pressure lowering effect of ramipril is not supported by an inhibition of presynaptic noradrenaline release.
Dominiak
P
P
Department of Pharmacology, Medical University of Lübeck, FRG.
Blöchl
A
A
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000378:metabolism*; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000008:administration & dosage; D002395:Catecholamines / Q000378:metabolism*; D003345:Corticosterone / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004837:Epinephrine / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D017257:Ramipril; D051381:Rats; D011918:Rats, Inbred SHR; D014403:Tubocurarine / Q000494:pharmacology; D014628:Vagotomy
D000806:Angiotensin-Converting Enzyme Inhibitors; D001643:Bridged Bicyclo Compounds; D002395:Catecholamines; D000804:Angiotensin II; D017257:Ramipril; D003891:Desipramine; D003345:Corticosterone; D014403:Tubocurarine; D009638:Norepinephrine; D004837:Epinephrine