title: Role of alpha(2)-adrenergic receptor subtypes in the acute hypertensive response to hypertonic saline infusion in anephric mice.
abstract: Experimental evidence suggests that the acute hypertensive response induced in anephric animals by infusion of a hypertonic saline solution is mediated by disinhibition of the presynaptic sympathoinhibitory alpha(2)-adrenergic receptors (alpha(2)-AR) of the central nervous system. The purpose of the present experiments was to dissect the role of the 3 distinct alpha(2)-AR subtypes (alpha(2A)-, alpha(2B), - and alpha(2C)-AR) in this response. Groups of genetically engineered mice deficient in each one of these alpha(2)-AR subtype genes were submitted to bilateral nephrectomy followed by a 0.4-mL infusion of 4% saline over a 2-hour period, with constant direct blood pressure (BP) monitoring. The alpha(2A)-AR-deficient and alpha(2C)-AR-deficient mice responded with significant BP elevations (by 11.8+/-2.5 and 16.7+/-1.7 mm Hg, respectively), and so did their wild-type counterparts (17.8+/-2.5 and 11.8+/-2.0 mm Hg, respectively) and the wild-type alpha(2B) +/+ (13.1+/-2.4 mm Hg). However, the alpha(2B)-AR-deficient mice were unable to raise their BP and had a slightly lowered BP (by -3.0+/-4. 0 mm Hg) at the end of the infusion period. All 6 groups exhibited elevated plasma norepinephrine levels ranging between 0.8 and 1.8 ng/mL at the end of the infusion. In all cases, the alpha(2)-AR-deficient groups tended to have higher norepinephrine levels than their wild-type counterparts. Surprisingly, this difference was significant only in the alpha(2B)-AR-deficient mice, which, despite the elevated norepinephrine, were unable to raise their BP. The data suggest that a full complement of the alpha(2B)-AR is needed to mediate the hypertensive response to acute saline load, even though its absence does not prevent the release of norepinephrine under these conditions.
authors.affiliation: Hypertension and Atherosclerosis Section of the Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: K P
authors.initials: KP
authors.lastname: Makaritsis
authors.forename: C
authors.initials: C
authors.lastname: Johns
authors.forename: I
authors.initials: I
authors.lastname: Gavras
authors.forename: H
authors.initials: H
authors.lastname: Gavras
mesh_terms: D000208:Acute Disease; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002395:Catecholamines / Q000097:blood; D004837:Epinephrine / Q000097:blood; D005838:Genotype; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*; D006982:Hypertonic Solutions; D007262:Infusions, Intravenous; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009392:Nephrectomy; D009638:Norepinephrine / Q000097:blood; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000502:physiology; D012965:Sodium Chloride / Q000008:administration & dosage*
chemical_list: D002395:Catecholamines; D006982:Hypertonic Solutions; D020033:Protein Isoforms; D018341:Receptors, Adrenergic, alpha-2; D011993:Recombinant Fusion Proteins; D012965:Sodium Chloride; D009638:Norepinephrine; D004837:Epinephrine