Effects of angiotensin II and angiotensin-(1-7) on the release of [3H]norepinephrine from rat atria.
We examined the effects of angiotensin II (Ang II) and Ang-(1-7) on the release of [3H]norepinephrine elicited by nerve stimulation (2 Hz, 0.5 millisecond, for 2 minutes) in rat atria isolated with their cardioaccelerans nerves. The stimulation-induced release of [3H]norepinephrine was increased 50% by 3 x 10(-8) mol/L of either peptide. No further increase in [3H]norepinephrine release was observed with peptide concentrations up to 3 x 10(-7) mol/L. This effect was completely blocked by the nonselective angiotensin receptor antagonist saralasin (1 x 10(-7) mol/L). The type 1 angiotensin receptor antagonist DuP 753 (1 x 10(-6) mol/L) entirely prevented the increases in [3H]norepinephrine caused by Ang II and Ang-(1-7). On the other hand, the type 2 angiotensin receptor antagonist PD 123319 (1 x 10(-6) mol/L) prevented the increase in [3H]norepinephrine release elicited by Ang-(1-7) but not by Ang II. These results suggest that Ang-(1-7), like Ang II, could have a neuromodulatory function in rat atria via activation of specific angiotensin receptor subtypes, which could be the subtype 1 angiotensin receptor for Ang II and subtypes 1 and 2 for Ang-(1-7).
Gironacci
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MM
Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Adler-Graschinsky
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E
Peña
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C
Enero
M A
MA
D000803:Angiotensin I; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000294:innervation; D006325:Heart Atria / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000187:drug effects; D012504:Saralasin / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D010446:Peptide Fragments; D011725:Pyridines; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C073402:PD 123319; D000803:Angiotensin I; D012504:Saralasin; C118790:angiotensin I (1-7); D019808:Losartan; D009638:Norepinephrine