Participation of prostaglandins and bradykinin in the effects of angiotensin II and converting enzyme-inhibition on sympathetic neurotransmission in vivo.
We investigated the mechanism(s) by which angiotensin converting enzyme (ACE)-inhibition and angiotensin (Ang) II influence peripheral sympathetic neurotransmission in canine gracilis muscle in situ, with alpha-adrenoceptors either intact or irreversibly blocked by phenoxybenzamine. ACE-inhibition by ramiprilat reduced, and subsequent infusion of Ang II (30 ng kg-1 min-1 i.v.) markedly increased arterial plasma Ang-(1-8)octapeptide levels, basal muscle perfusion pressures and mean arterial pressure. Local intra-arterial bolus injection of Ang II caused marked vasoconstriction followed by vasodilation. This vasoconstrictor response was enhanced and the ensuing vasodilation was abolished following prostaglandin synthesis inhibition by diclofenac. The vasoconstrictor response to low frequency (0.5 Hz) sympathetic nerve stimulation was also enhanced by diclofenac. The nerve stimulation-evoked noradrenaline (NA) overflow was reduced by ramiprilat when alpha-adrenoceptors were blocked (-11 +/- 3%, P < 0.05), but increased when alpha-adrenoceptors were intact (+28 +/- 14%, P < 0.05). During ACE-inhibition, effective bradykinin receptor antagonism by HOE 140 reduced stimulation-evoked NA overflow irrespective of alpha-adrenoceptor blockade (i.e. by 25 +/- 5 and 20 +/- 3% in the absence and presence of alpha-adrenoceptor blockade, respectively, P < 0.01). Diclofenac increased stimulation-evoked NA overflow in the absence of alpha-adrenoceptor blockade (+ 19 +/- 4%, P < 0.05). IV infusion of Ang II failed to enhance stimulation-evoked NA overflow both before and after diclofenac.(ABSTRACT TRUNCATED AT 250 WORDS)
Schwieler
J H
JH
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Kahan
T
T
Nussberger
J
J
Hjemdahl
P
P
D000804:Angiotensin II / Q000097:blood / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D065168:Bradykinin Receptor Antagonists; D004008:Diclofenac / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D009638:Norepinephrine / Q000378:metabolism; D010477:Perfusion; D011453:Prostaglandins / Q000097:blood / Q000502:physiology*; D017257:Ramipril / Q000031:analogs & derivatives* / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D065168:Bradykinin Receptor Antagonists; D011453:Prostaglandins; D000804:Angiotensin II; D004008:Diclofenac; C052549:ramiprilat; C065679:icatibant; D017257:Ramipril; D001920:Bradykinin; D009638:Norepinephrine