Studies on the peptides encoded by rat and human angiotensin II complementary RNA.
Some evidence suggests that RNA complementary to the messenger RNA encoding a peptide hormone encodes a complementary peptide that binds the original peptide hormone. The objective of this investigation was to assess in vivo the ability of complementary angiotensin II (II Ang) peptides to block the biological effects of angiotensin II (Ang II). Increasing concentrations of rat or human II Ang were preincubated with Ang II for 2 hours, and this solution was then infused intra-arterially into the superior mesenteric artery. Human, but not rat, II Ang dose-dependently inhibited Ang II-induced mesenteric vasoconstriction. The in vivo inhibitory potencies of human II Ang and [Sar1,Ile8]Ang II, with respect to inhibition of the pressor response to Ang II, were compared by infusing intravenously increasing doses of each blocker and determining their effects on a fixed intravenous dose of Ang II. Although human II Ang could abolish the pressor response to Ang II, [Sar1,Ile8]Ang II was approximately 100 times more potent in this regard. A fixed dose of human II Ang (150 micrograms/min i.v.) inhibited the effects of increasing doses of Ang II on mesenteric vascular resistance, arterial blood pressure, and aldosterone secretion. The 1H nuclear magnetic resonance spectra of human II Ang and Ang II were determined both separately and when combined in the same cuvette. The spectrum obtained by overlaying the separate spectra for these two peptides was the same as the spectrum obtained from the mixture of these two peptides in the same cuvette.(ABSTRACT TRUNCATED AT 250 WORDS)
Jackson
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Center for Clinical Pharmacology, University of Pittsburgh Medical Center, PA 15261.
Prakash
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Blair
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D000804:Angiotensin II / Q000235:genetics / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D012313:RNA / Q000378:metabolism*; D018075:RNA, Complementary; D051381:Rats; D017207:Rats, Sprague-Dawley
D018075:RNA, Complementary; D000804:Angiotensin II; D012313:RNA