Influence of the renin-angiotensin system on sympathetic neurotransmission in canine skeletal muscle in vivo.
The physiological importance of interactions between angiotensin II and sympathetic neurotransmission was studied in an in vivo model with constant flow blood perfused gracilis muscle in situ in dogs pretreated with desipramine and atropine. Sympathetic nerve stimulation-(2 and 8 Hz, 480 pulses) evoked over-flow of endogenous noradrenaline and vasoconstriction, and vasoconstrictor responses to exogenous noradrenaline (0.5 nmol, locally i.a.) were evaluated. Angiotensin converting enzyme inhibition by benazeprilat (10 mg i.v.; n = 8) reduced arterial angiotensin II levels from 26 +/- 8 to 2 +/- 1 pM and reduced mean arterial and basal muscle perfusion pressures. Subsequent resubstitution of angiotensin II (3, 30 and 90 ng kg-1 min-1 i.v.) elevated arterial angiotensin II dose-dependently (to 67 +/- 14, 622 +/- 63 and 1940 +/- 251 pM, respectively), as well as mean arterial and muscle perfusion pressures. Nerve stimulation-evoked noradrenaline overflow was unchanged following benazeprilat (-4 +/- 4 and +1 +/- 8% at 2 and 8 Hz, respectively) and during subsequent infusions of angiotensin II. Vasoconstrictor responses to nerve stimulation and exogenous noradrenaline were also uninfluenced by these treatments. Thus, angiotensin II did not enhance sympathetic neurotransmission at the postjunctional level. Another group of animals was pretreated with noncompetitive alpha-adrenoceptor blockade locally by phenoxybenzamine and benextramine (0.5 mg kg-1 i.a. of each; n = 7), which abolished vasoconstrictor responses to nerve stimulation. The effects of benazeprilat and subsequent angiotensin II infusions (3 and 30 ng kg-1 min-1 i.v.) on circulating angiotensin II levels, mean arterial and muscle perfusion pressures were similar in this group.(ABSTRACT TRUNCATED AT 250 WORDS)
Schwieler
J H
JH
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Kahan
T
T
Nussberger
J
J
Hjemdahl
P
P
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D009132:Muscles / Q000294:innervation*; D010643:Phenoxybenzamine / Q000494:pharmacology; D012084:Renin-Angiotensin System / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D010643:Phenoxybenzamine; C052133:benazeprilat