title: Effects of sodium restriction and cyclooxygenase-2 inhibition on the course of hypertension, proteinuria and cardiac hypertrophy in Ren-2 transgenic rats.
abstract: The present study was performed to evaluate the effects of sodium intake and of chronic cyclooxygenase-2 (COX-2) inhibition on systolic blood pressure (SBP) in heterozygous male transgenic rats harboring the mouse Ren-2 renin gene (TGR) and in transgene-negative normotensive Hannover Sprague-Dawley (HanSD). Twenty-eight days old TGR and HanSD were randomly assigned to groups fed either normal salt (NS) or low sodium (LS) diets. COX-2 blockade was achieved with NS-398 (1 mg x kg(-1).day(-1) in drinking water). During an experimental period of 26 days, SBP was repeatedly measured by tail plethysmography in conscious animals. We found that the LS diet prevented the development of hypertension in TGR and did not change SBP in HanSD. Low sodium intake also prevented proteinuria and cardiac hypertrophy in TGR. On the other hand, irrespective of sodium intake chronic COX-2 inhibition did not alter the course of SBP in either TGR or HanSD. The present data indicate that TGR exhibit an important salt-sensitive component in the developmental phase of hypertension. They also suggest that systemic COX-2-derived prostaglandins do not act as vasodilatory counterregulatory agents in TGR in which an exaggerated vascular responsiveness to angiotensin II is assumed as the pathophysiological mechanism in the development of hypertension.
authors.affiliation: Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Vídenská 1958/9, CZ-140 21 Prague 4, Czech Republic. ivvn@medicon.cz
authors.forename: I
authors.initials: I
authors.lastname: Vanecková
authors.forename: P
authors.initials: P
authors.lastname: Skaroupková
authors.forename: P
authors.initials: P
authors.lastname: Dvorák
authors.forename: V
authors.initials: V
authors.lastname: Certíková Chábová
authors.forename: V
authors.initials: V
authors.lastname: Tesar
authors.forename: M
authors.initials: M
authors.lastname: Bader
authors.forename: D
authors.initials: D
authors.lastname: Ganten
authors.forename: H J
authors.initials: HJ
authors.lastname: Kramer
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006977:Hypertension, Renal / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009578:Nitrobenzenes / Q000494:pharmacology; D009929:Organ Size; D011507:Proteinuria / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000235:genetics*; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D017673:Sodium Chloride, Dietary; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D012083:Renin