Differential effects of alpha-adrenoceptor agonists on human retinal microvessel diameter.
The effects of locally administered brimonidine, clonidine, and p-aminoclonidine on microvessel caliber were compared in human retinal tissues grafted into the hamster cheek pouch. Clonidine and p-aminoclonidine, but not brimonidine, potently constricted human retinal microvessels over a broad concentration range. All three agonists elicited significant vasoconstriction in naive hamster cheek pouch microvasculature. The alpha2-adrenoceptor antagonist, rauwolscine, inhibited p-aminoclonidine-induced constriction in naive hamster cheek pouch microvessels, but not p-aminoclonidine-induced effects in retinal grafts. Selective alpha1-adrenoceptor agonists evoked vasoconstriction in retinal grafts only at relatively high concentrations. These differential effects on the retinal microvasculature could not be readily explained solely on the basis of alpha1- or alpha2-adrenoceptor involvement. Clonidine, p-aminoclonidine and brimonidine are also imidazoline derivatives that interact with putative non-adrenergic imidazoline-sensitive binding sites, the so-called I1-imidazoline binding site subtype implicated by some investigators in mediation of peripheral vasoconstriction. As with p-aminoclonidine, the potent vasoconstriction in human retinal microvasculature elicited by moxonidine, an alpha-adrenergic agonist that has also been reported to exhibit selectivity for putative I1-imidazoline binding sites, was not inhibited by the selective alpha-adrenoceptor antagonist, rauwolscine, nor by idazoxan, an antagonist characterized as having substantial activity at putative I2-imidazoline binding sites. These data suggest the possible involvement of an unconventional non-adrenergic imidazoline-sensitive pathway in regulation of microvascular responses in the inner retina, and that drug activity mediated via such an imidazoline-sensitive component could potentially evoke deleterious effects in the retinal microvasculature.
Spada
C S
CS
Department of Biological Sciences, Pharmaceutical Research & Development, Allergan, Inc., Irvine, California 92612-1599, USA. spada_clayton@allergan.com
Nieves
A L
AL
Burke
J A
JA
Wheeler
L A
LA
Woodward
D F
DF
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000068438:Brimonidine Tartrate; D002610:Cheek / Q000601:surgery; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006224:Cricetinae; D006801:Humans; D008647:Mesocricetus; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology*; D012160:Retina / Q000637:transplantation; D012171:Retinal Vessels / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011810:Quinoxalines; D000068438:Brimonidine Tartrate; C016986:apraclonidine; D003000:Clonidine