Effect of locally generated angiotensin II on noradrenergic neuroeffector function in the rat isolated caudal artery.
The effects of angiotensin II and its precursors angiotensin I and tetradecapeptide renin substrate were investigated in isolated segments of the rat caudal artery. Each peptide constricted the rat caudal artery and also enhanced vasoconstrictor responses to sympathetic nerve stimulation (0.5 Hz, 10 s). The threshold concentrations for each peptide in enhancing sympathetic vasoconstrictor responses were lower than those required to produce vasoconstriction. Tetradecapeptide renin substrate was the least potent of the three peptides and had the slowest onset of action. Angiotensin II and angiotensin I each enhanced noradrenergic transmission to the same degree, whether perfused through the lumen or added to the adventitial surface of the artery. In contrast, tetradecapeptide renin substrate was more potent when applied to the adventitial surface. The effects of angiotensin I were blocked by the converting enzyme inhibitor enalaprilat, whereas the effects of tetradecapeptide renin substrate were unaltered by enalaprilat, or by the renin inhibitors pepstatin or a decapeptide renin inhibitor. These findings suggest that tetradecapeptide renin substrate and angiotensin I may be converted to angiotensin II within the rat caudal artery, with subsequent enhancement of noradrenergic neuroeffector function. However, the enzyme responsible for the conversion of tetradecapeptide renin substrate cannot be determined from the present findings.
D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000096:biosynthesis / Q000494:pharmacology*; D000808:Angiotensinogen / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects; D004656:Enalapril / Q000031:analogs & derivatives / Q000494:pharmacology; D015773:Enalaprilat; D005260:Female; D008297:Male; D018377:Neurotransmitter Agents / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013623:Tail / Q000098:blood supply*
D018377:Neurotransmitter Agents; D009842:Oligopeptides; D000808:Angiotensinogen; D000804:Angiotensin II; D004656:Enalapril; C027509:renin inhibitory peptide; D000803:Angiotensin I; D015773:Enalaprilat