alpha(2)-adrenergic receptors are not required for central anti-hypertensive action of moxonidine in mice.
In the mouse medulla oblongata, we characterized binding properties and functional responses of two recognition sites for imidazoline compounds: I(1)-imidazoline and alpha(2)-adrenergic receptors. The mouse medulla expresses a higher density of I(1)-receptors than in the rat, whereas alpha(2)-receptor densities were similar between the two species. In anesthetized, ventilated and paralyzed mice, we tested the hypotensive actions of the I(1)/alpha(2) agonist moxonidine, determined its central site of its actions, and the relative roles of I(1) and alpha(2)-receptors. Experiments were performed in C(57)Bl(6) wild type and alpha(2A)-adrenergic receptor deficient mice. In both types of mice, neuronal activation within the rostral ventrolateral medulla (RVLM) region by glutamate microinjection elicited increases in arterial pressure. Moxonidine (0.5 nmol/site/10 nl) microinjected bilaterally into this vasopressor region decreased arterial pressure by 30% and heart rate by 11% in wild type mice. Efaroxan, the I(1)/alpha(2) antagonist (0.4 nmol) when microinjected into the RVLM elevated blood pressure itself and abolished the action of moxonidine, whereas alpha(2)-blockade with SK&F 86466 had no significant effect on blood pressure and did not attenuate moxonidine's effect. To more definitively test the role of alpha(2)-adrenergic receptors in the action of moxonidine, moxonidine was microinjected into the RVLM of alpha(2A)-adrenergic deficient mice. The decreases in arterial pressure were nearly identical to those of wild type mice, whereas bradycardia was attenuated. Thus, in the mouse moxonidine acts within the RVLM region to lower arterial pressure mainly through the I(1)-imidazoline receptor independent of alpha(2)-adrenergic receptors.
Tolentino-Silva
F P
FP
Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo, Brazil.
Haxhiu
M A
MA
Waldbaum
S
S
Dreshaj
I A
IA
Ernsberger
P
P
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000679:Amygdala / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology; D001667:Binding, Competitive; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D018698:Glutamic Acid / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy; D007093:Imidazoles / Q000494:pharmacology*; D054755:Imidazoline Receptors; D007275:Injections, Intravenous; D008526:Medulla Oblongata / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008845:Microinjections; D011149:Pons / Q000737:chemistry / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics* / Q000378:metabolism*; D011955:Receptors, Drug / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D001572:Benzofurans; D007093:Imidazoles; D054755:Imidazoline Receptors; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; D018698:Glutamic Acid; C043482:moxonidine; C062597:efaroxan