title: alpha(1)-adrenoceptor subtypes in rat renal resistance vessels: in vivo and in vitro studies.
abstract: This study provides new information about the relative importance of different alpha(1)-adrenoceptors during norepinephrine (NE) activation in rat renal resistance vessels. In Sprague-Dawley rats, we measured renal blood flow (RBF) using electromagnetic flowmetry in vivo and the intracellular free calcium concentration ([Ca(2+)](i)) utilizing ratiometric photometry of fura 2 fluorescence in isolated afferent arterioles. Renal arterial bolus injection of NE produced a transient 46% decrease in RBF. In microdissected afferent arterioles, NE (1 microM) elicited an immediate square-shaped increase in [Ca(2+)](i), from 90 to 175 nM (P < 0.001). Chloroethylclonidine (CEC) (50 microM) had no chronic irreversible alkylating effect in vitro but exerted acute reversible blockade on norepinephrine (NE) responses both on [Ca(2+)](i) in vitro and on RBF in vivo. The RBF response was attenuated by approximately 50% by the putative alpha(1A)-adrenoceptor and alpha(1D)-adrenoceptor antagonists 5-methylurapidil (5-MU), and 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4. 5]decane-7,9-dione dihydrochloride (BMY-7378) (12.5 and 62.5 microg/h), respectively. The in vitro [Ca(2+)](i) response to NE was blocked approximately 25% and 50% by 5-MU (100 nM and 1 microM). BMY-7378 (100 nM and 1 microM) attenuated the NE-induced response by approximately 40% and 100%. The degree of inhibition in vitro was similar to the in vivo experiments. In conclusion, 5-MU and BMY-7378 attenuated the NE-induced responses, although relatively high concentrations were required, suggesting involvement of both the alpha(1A)-adrenoceptor and alpha(1D)-adrenoceptor. Participation of the alpha(1B)-adrenoceptor is less likely, as we found no evidence for CEC-induced alkylation.
authors.affiliation: Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7545, USA.
authors.forename: M
authors.initials: M
authors.lastname: Salomonsson
authors.forename: K
authors.initials: K
authors.lastname: Brännström
authors.forename: W J
authors.initials: WJ
authors.lastname: Arendshorst
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1; C051731:chlorethylclonidine; D003000:Clonidine; D002118:Calcium; D009638:Norepinephrine