Premium
The α 1B ‐adrenoceptor subtype mediates adrenergic vasoconstriction in mouse retinal arterioles with damaged endothelium
Author(s) -
Böhmer Tobias,
Manicam Caroline,
Steege Andreas,
Michel Martin C,
Pfeiffer Norbert,
Gericke Adrian
Publication year - 2014
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12743
Subject(s) - phenylephrine , vasoconstriction , endothelium , retinal , adrenergic receptor , endocrinology , medicine , prazosin , biology , arteriole , adrenergic , circulatory system , receptor , antagonist , blood pressure , biochemistry
Background and Purpose The α 1 ‐adrenoceptor family plays a critical role in regulating ocular perfusion by mediating responses to catecholamines. The purpose of the present study was to determine the contribution of individual α 1 ‐adrenoceptor subtypes to adrenergic vasoconstriction of retinal arterioles using gene‐targeted mice deficient in one of the three adrenoceptor subtypes (α 1 A ‐ AR −/− , α 1 B ‐ AR −/− and α 1 D ‐ AR −/− respectively). Experimental Approach Using real‐time PCR , m RNA expression for individual α 1 ‐adrenoceptor subtypes was determined in murine retinal arterioles. To assess the functional relevance of the three α 1 ‐adrenoceptor subtypes for mediating vascular responses, retinal vascular preparations from wild‐type mice and mice deficient in individual α 1 ‐adrenoceptor subtypes were studied in vitro using video microscopy. Key Results Retinal arterioles expressed m RNA for all three α 1 ‐adrenoceptor subtypes. In functional studies, arterioles from wild‐type mice with intact endothelium responded only negligibly to the α 1 ‐adrenoceptor agonist phenylephrine. In endothelium‐damaged arterioles from wild‐type mice, phenylephrine evoked concentration‐dependent constriction that was attenuated by the α 1 ‐adrenoceptor blocker prazosin. Strikingly, phenylephrine only minimally constricted endothelium‐damaged retinal arterioles from α 1 B ‐ AR −/− mice, whereas arterioles from α 1 A ‐ AR −/− and α 1 D ‐ AR −/− mice constricted similarly to arterioles from wild‐type mice. Constriction to U 46619 was similar in endothelium‐damaged retinal arterioles from all four mouse genotypes. Conclusions and Implications The present study is the first to demonstrate that α 1 ‐adrenoceptor‐mediated vasoconstriction in murine retinal arterioles is buffered by the endothelium. When the endothelium is damaged, a vasoconstricting role of the α 1 B ‐adrenoceptor subtype is unveiled. Hence, the α 1 B ‐adrenoceptor may represent a target to selectively modulate retinal blood flow in ocular diseases associated with endothelial dysfunction.