title: Examination by radioligand binding of the alpha1 adrenoceptors in the mesenteric arterial vasculature during the development of salt-sensitive hypertension.
abstract: Previous experiments have suggested that the vascular smooth muscle of Dahl salt-sensitive (DS) rats may possess a difference in the alpha1-adrenoceptor population or its transduction processes compared to Dahl salt-resistant (DR) rats. The purpose of the current research is to study the role of alpha1-adrenoceptors in the specific supersensitivity to norepinephrine (NE) seen prior to and early in the development of hypertension in the DS rat. Experiments in isolated perfused superior mesenteric arterial vasculature from DS rats chronically fed a high (7%) salt diet for 5 days or 3 weeks, in the absence or presence of an elevation in systolic blood pressure, respectively, demonstrated a specific supersensitivity to NE relative to DR rats. The enhanced responsiveness was specific to NE after 5 days of high salt since no differences in sensitivity of these preparations was observed to either KCl or 5-HT. A small but significant elevation in sensitivity to KCl following 3 weeks of treatment suggests that multiple factors may contribute to tissue responsiveness at this time. Radioligand binding experiments were performed using [125I]-HEAT to study the alpha1-adrenoceptor population and its subtypes. Saturation experiments using membranes prepared from the superior mesenteric arterial vasculature or mesenteric arterial branches showed no significant differences in overall alpha1-adrenoceptor population between DS and DR rats fed a high-salt diet for 5 days or 3 weeks. Competition experiments using membranes prepared from the superior mesenteric arterial branches in the presence of the alpha1A-subtype selective antagonist 5-methylurapidil showed two binding sites (high and low affinity) in these resistance vessels but no significant differences in nature or ratio of these sites between the DS and DR groups. These results suggest that changes in the alpha1-adrenoceptor population are not responsible for the specific supersensitivity to NE, which may be an early event in the induction and development of hypertension.
authors.affiliation: Department of Pharmacology and Toxicology, West Virginia University Robert C. Byrd Health Sciences Center, Morgantown 26506-9223, USA.
authors.forename: S W
authors.initials: SW
authors.lastname: Caveney
authors.forename: D A
authors.initials: DA
authors.lastname: Taylor
authors.forename: W W
authors.initials: WW
authors.lastname: Fleming
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D006973:Hypertension / Q000209:etiology / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010627:Phenethylamines / Q000378:metabolism; D010879:Piperazines / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D044024:Tetralones
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D010627:Phenethylamines; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D017673:Sodium Chloride, Dietary; D044024:Tetralones; C057446:5-methylurapidil; D012701:Serotonin; D011189:Potassium Chloride; C048008:2-(beta-(3-iodo-4-hydroxyphenyl)ethylaminomethyl)tetralone; D009638:Norepinephrine