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 a‐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 a‐adrenoceptors were blocked (‐ 11 ± 3 %, P < 0.05), but increased when a‐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 a‐adrenoceptor blockade (i.e. by 25 ± 5 and 20 ± 3% in the absence and presence of a‐adrenoceptor blockade, respectively, p < 0.01). Diclofenac increased stimulation‐evoked NA overflow in the absence of a‐adrenoceptor blockade (+ 19 ± 4%, P < 0.05). I.v. infusion of Ang II failed to enhance stimulation‐evoked NA overflow both before and after diclofenac. In conclusion, the results support the ideas that local formation of Ang II and bradykinin facilitate, and of prostaglandins inhibit NA release, and that ACE inhibition influences sympathetic neurotransmission through all of these mechanisms in skeletal muscle in situ; the net result depends on the degree of prejunctional a‐adrenergic feedback inhibition. Circulating Ang II may enhance the local formation of vasodilatory prostaglandins, but does not seem to modulate NA release even after prostaglandin synthesis inhibition in this model. Our data suggest that circulating Ang II may not reach the perivascular sympathetic nerves to a significant extent in skeletal muscle in vivo.