Article: article from journal or magazin.
Converting enzyme inhibition modulates sympathetic neurotransmission in vivo via multiple mechanisms
American Journal of Physiology. Endocrinology and Metabolism
4 Pt 1
Comparative Study Journal Article Research Support, Non-U.S. Gov't --- Old month value: Apr
We investigated the mechanism(s) by which angiotensin-converting enzyme (ACE) inhibition influences peripheral sympathetic neurotransmission. Thus effects of the angiotensin II (ANG II) receptor antagonist losartan (Du Pont 753) were compared with those of the ACE inhibitor benazeprilat on sympathetic neurotransmission in canine gracilis muscle in situ, with alpha-adrenoceptors either intact or irreversibly blocked by phenoxybenzamine. Furthermore, effects of the bradykinin receptor antagonist HOE 140 and the prostaglandin synthesis inhibitor diclofenac were studied after ACE inhibition. Losartan reduced the vasoconstrictor response to exogenous ANG II by 76 +/- 4% at the dose used and lowered muscle perfusion pressures. ACE inhibition by benazeprilat reduced plasma ANG-(1-8) octapeptide levels (from 8 +/- 2 to 2 +/- 1 pM), mean arterial pressure, and muscle perfusion pressures. After ACE inhibition, both HOE 140 (at a dose that reduced the vasodilatory response to exogenous bradykinin by 80 +/- 3%) and diclofenac elevated basal perfusion pressures. Losartan reduced the nerve stimulation-evoked overflow of endogenous norepinephrine (NE) (-14 +/- 6%) and vasoconstrictor responses (alpha-adrenoceptors intact). ACE inhibition increased NE overflow when alpha-adrenoceptors were intact (+12 +/- 5%) and tended to reduce it when alpha-adrenoceptors were blocked (-12 +/- 4%). During ACE inhibition, HOE 140 reduced and diclofenac enhanced the evoked NE overflow. In the absence of ACE inhibition, neither HOE 140 nor diclofenac influenced NE overflow. Our findings indicate that ACE inhibition influences sympathetic neurotransmission via reduced ANG II formation and enhanced bradykinin and prostaglandin accumulation. The effects of ANG II on sympathetic neurotransmission are, however, small under these in vivo conditions.
Angiotensin II/antagonists & inhibitors/pharmacology Angiotensin-Converting Enzyme Inhibitors/*pharmacology Animals Benzazepines/*pharmacology Biphenyl Compounds/*pharmacology Blood Pressure/*drug effects Bradykinin/analogs & derivatives/antagonists & inhibitors/pharmacology Diclofenac/pharmacology Dogs Epinephrine/pharmacology Female Imidazoles/*pharmacology Losartan Muscle Denervation Muscles/drug effects/innervation/physiology Norepinephrine/blood Phenoxybenzamine/pharmacology Receptors, Angiotensin/antagonists & inhibitors Sympathetic Nervous System/drug effects/*physiology Synaptic Transmission/*drug effects Tetrazoles/*pharmacology
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