title: AT(1) receptor regulation in salt-sensitive hypertension.
abstract: The molecular events governing salt-sensitive hypertension are currently unknown. Because the renin-ANG system plays a central role in blood pressure regulation and electrolyte balance, it may be closely involved in the phenomenon of salt sensitivity. Therefore, we examined the effect of a high-salt diet (8%) and a low-salt diet (0.4%) on ANG II-caused vascular constriction and ANG II type 1 (AT(1)) receptor expression in aorta, brain, and kidney of Dahl S (salt-sensitive) and Dahl R (salt-resistant) rats by means of radioligand binding assays and quantitative PCR. NaCl diet at 8% led to a significant increase of blood pressure in Dahl S but not in Dahl R rats. High-sodium intake caused a profound decrease of ANG II-induced aortic vasoconstriction in both Dahl R and Dahl S rats. The underlying mechanism was a downregulation of aortic AT(1) receptor density and AT(1) receptor mRNA. AT(1) receptor mRNA was downregulated to 57.8% in Dahl R and 59.0% in Dahl S rats by an 8% NaCl diet compared with a 0.4% NaCl diet (P < 0.05). There was a similar decrease in aortic AT(1) receptor density. Additionally, AT(1) receptor mRNA was also downregulated in the kidney but upregulated the brain of Dahl R and S rats on a high-salt diet. Thus high NaCl intake causes organ-specific AT(1) receptor regulation in Dahl R and in Dahl S rats despite the differential blood pressure regulation in these animal models in response to a high-salt diet. These findings suggest that the regulation of vascular AT(1) receptors is influenced by numerous factors such as the renin-ANG system and obviously by various other events that are currently only partly understood.
authors.affiliation: Klinik III für Innere Medizin, Universität Köln, 50924 Köln, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Strehlow
authors.forename: G
authors.initials: G
authors.lastname: Nickenig
authors.forename: J
authors.initials: J
authors.lastname: Roeling
authors.forename: S
authors.initials: S
authors.lastname: Wassmann
authors.forename: O
authors.initials: O
authors.lastname: Zolk
authors.forename: A
authors.initials: A
authors.lastname: Knorr
authors.forename: M
authors.initials: M
authors.lastname: Böhm
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D004039:Diet, Sodium-Restricted; D004351:Drug Resistance; D006973:Hypertension / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics / Q000378:metabolism*; D012083:Renin / Q000097:blood; D012965:Sodium Chloride / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D012965:Sodium Chloride; D012083:Renin