Participation of angiotensin receptors in acute hypoxia in mice. I. Effects of angiotensin peptide receptor ligands saralasin and sarmesin.
The effects of angiotensin II (Ang II) and angiotensin receptor ligands sarmesin ([Sar1, Tyr(Me)4] Ang II) and saralasin ([Sar1, Ala8] Ang II) administered intracerebroventricularly (i.c.v.) on acute anoxic hypoxia were studied in mice. The interactions of these ligands and of amastatin (an aminopeptidase A inhibitor) after pretreatment with Ang II and sarmesin, respectively, were also studied. Ang II decreased the latency to hypoxia-induced convulsive seizures and altered survival time (increase or decrease depending on the dose). Sarmesin and saralasin significantly increased the latency to seizures as well as survival time. Pretreatment with saralasin and sarmesin antagonized the Ang II effect on the latency to seizures. Both drugs increased the Ang II effect on the survival time. Amastatin tended to increase the effect of sarmesin on the survival time. Taken together, the results suggest that the antihypoxic effect of sarmesin and saralasin is most likely due to an action on Ang II receptors, with the agents behaving as partial agonists.
Georgiev
V
V
Laboratory of Experimental Psychopharmacology, Bulgarian Academy of Sciences, Sofia, Bulgaria. georgiev@iph.bio.bas.bg
Opitz
M
M
D000208:Acute Disease; D000804:Angiotensin II / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002534:Hypoxia, Brain / Q000188:drug therapy* / Q000378:metabolism; D007276:Injections, Intraventricular; D008024:Ligands; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011945:Receptors, Angiotensin / Q000378:metabolism / Q000502:physiology*; D012504:Saralasin / Q000378:metabolism / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D008024:Ligands; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C040420:angiotensin II, Sar(1)-Me-Tyr(4)-; D012504:Saralasin