Dose-dependent inhibitory effects of angiotensin II on visual responses of the rat superior colliculus: AT1 and AT2 receptor contributions.
Angiotensin II (Ang II) has traditionally been regarded as a peripherally circulating and acting hormone involved in fluid homeostasis and blood pressure regulation. With the rather recent localization of Ang II receptors within the mammalian brain, renewed interest has emerged in the hope of elucidating the central impact and function of this hormone. One region that has been clearly demonstrated to express Ang II receptors is the superior colliculus (SC). This mesencephalic structure plays an important role in sensory visuomotor integration. Receptors for Ang II (of both the AT1 and AT2 subtypes) have been localized within the superficial layers of this structure, i.e. the areas that are visually responsive. In the hopes of characterizing the role of Ang II in the SC, we have attempted to physiologically activate these receptors in vivo and observe the effects of Ang II on visually evoked responses. In the attempt to identify the receptor subtype(s) responsible in mediating these effects, Ang II was injected concomitantly with selective receptor ligands. Experiments were performed on adult rats prepared in classical fashion for electrophysiological studies. Through microinjection of Ang II, and the simultaneous recording of visually evoked potentials to flash stimulation, we have observed that this peptide yields a strong suppressive effect on visual neuronal activity. By injecting Ang II at various concentrations (10(-3)-10(-10) M), we have further observed that the effects of this peptide express a dose-related dependency. Injection of Ang II in progressively more ventral layers yielded less pronounced effects, demonstrating physiologically the discrete localization of these receptors in the stratum griseum superficiale. Coinjection of Ang II with Losartan yielded a near complete blockade of Ang II suppressive effects, suggesting that AT1 receptors play a prominent role in mediating these responses. However, coinjection of Ang II with PD 123,319 yielded a slight, yet significant partial blockade. Coinjection of Ang II with both the AT1 and AT2 receptor antagonists yielded a complete blockade of the Ang II effect. Finally, some of the results suggest that the AT2 receptor ligand CGP 42,112 may possess agonist properties. Taken together, these findings suggest that the AT1 receptor is predominantly involved in mediating Ang II responses in the SC and there also appears to be some indication of AT2 receptor involvement. However, the underlying mechanisms (such as receptor interactions), the exact specificity of the ligands used, and the possibility of other receptor subtype implication have yet to be explored fully.
Merabet
L
L
Département d'ophtalmologie, Faculté de médecine, Université de Sherbrooke, Québec, Canada.
de Gasparo
M
M
Casanova
C
C
D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005074:Evoked Potentials, Visual / Q000187:drug effects / Q000502:physiology*; D008636:Mesencephalon / Q000187:drug effects / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology*
D057911:Angiotensin Receptor Antagonists; D009842:Oligopeptides; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C060894:CGP 42112A