Modulation of adrenergic transmission by angiotensins in the perfused rat mesentery.
Isolated rat mesenteric arteries perfused with a modified Krebs solution were utilized to study the effects of angiotensin II (AII), angiotensin III (AIII), and [des-Asp1-Arg2]AII on adrenergic transmission. Angiotensin II potentiated vasoconstrictor responses to both sympathetic nerve stimulation and to exogenous norepinephrine, whereas AIII and [des-Asp1-Arg2]AII potentiated vasoconstrictor responses to exogenous norepinephrine only. When the responses to exogenous norepinephrine were compared, the order of agonist potency was AIII greater than AII greater than [des-Asp1-Arg2]AII. The potentiation of sympathetic nerve stimulation by AII was inhibited by simultaneous administration of AIII (25%), [des-Asp1-Arg2]AII (51%), [Sar1-Ile8]AII (83%), and (Ile7)AIII (80%). The potentiation of exogenous norepinephrine by AII, AIII, and [des-Asp1-Arg2]AII was inhibited by [Sar1-Ile8]AII (110%, 113%, and 108%, respectively) and by [Ile7]AIII (50%, 64%, 91%, respectively). We conclude that AII possesses the capacity both to increase norpinephrine release during sympathetic nerve stimulation and to decrease norepinephrine reuptake, whereas AIII and [des-Asp1-Arg2]AII decrease norepinephrine release and reuptake. Also, under conditions of increased N-terminal degradation of AII, blockade of norepinephrine reuptake would be increased while the release of norepinephrine by nerve stimulation would be reduced.
D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology; D000805:Angiotensin III / Q000494:pharmacology*; D000818:Animals; D008297:Male; D008638:Mesenteric Arteries / Q000294:innervation / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D013564:Sympathetic Nervous System / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014666:Vasomotor System / Q000187:drug effects*
D000804:Angiotensin II; D000805:Angiotensin III; D009638:Norepinephrine