title: Improvement of cardiovascular effects of metoprolol by replacement of common salt with a potassium- and magnesium-enriched salt alternative.
abstract: 1. The influence of sodium chloride (NaCl)-enrichment of the diet (6% of the dry weight) and that of a novel sodium-reduced, potassium-, magnesium-, and L-lysine-enriched salt alternative on the cardiovascular effects of the beta 1-adrenoceptor blocking drug, metoprolol, was studied in stroke-prone spontaneously hypertensive rats. 2. Increased dietary sodium chloride intake produced a marked rise in blood pressure and induced left ventricular and renal hypertrophy. By contrast, the salt alternative did not increase blood pressure and caused remarkably less cardiac and renal hypertrophy than did sodium chloride. 3. Metoprolol treatment at a daily dose of 250 mg kg-1 lowered blood pressure and decreased left ventricular hypertrophy index during the control diet. Sodium chloride-enrichment blocked the antihypertensive effect of metoprolol, while a partial protective effect on left ventricular and renal hypertrophy persisted. In the presence of the salt alternative-enrichment both at the level of 6% and 10.5% (corresponding to a NaCl level of 6%), metoprolol was fully able to exert its beneficial cardiovascular and renal effects. 4. Both salt supplementations, irrespective of metoprolol treatment, induced a 3 to 4 fold increase in the urinary excretion of calcium. There was a linear correlation between the urinary excretions of sodium and calcium. The urinary excretion of magnesium rose by 90% and that of potassium by 110% in the salt alternative group. 6. Our findings suggest that replacement of common salt by a potassium-, and magnesium-enriched salt alternative in the diet produces beneficial cardiovascular effects and improves the antihypertensive efficacy of metoprolol in stroke-prone spontaneously hypertensive rats. Increased intake of potassium and/or magnesium and L-lysine from the salt alternative is involved in the beneficial effects of the salt alternative. The NaCl-induced myocardial and renal hypertrophies appear to be partially mediated by Beta-adrenoceptor activation.
authors.affiliation: Department of Pharmacology and Toxicology, University of Helsinki, Finland.
authors.forename: E M
authors.initials: EM
authors.lastname: Mervaala
authors.forename: J
authors.initials: J
authors.lastname: Laakso
authors.forename: H
authors.initials: H
authors.lastname: Vapaatalo
authors.forename: H
authors.initials: H
authors.lastname: Karppanen
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002561:Cerebrovascular Disorders / Q000401:mortality / Q000517:prevention & control; D004435:Eating / Q000187:drug effects; D004573:Electrolytes / Q000652:urine; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology / Q000517:prevention & control; D007668:Kidney / Q000187:drug effects; D015636:Magnesium Chloride / Q000494:pharmacology*; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D012982:Sodium, Dietary / Q000494:pharmacology*
chemical_list: D004573:Electrolytes; D012982:Sodium, Dietary; D015636:Magnesium Chloride; D011189:Potassium Chloride; D008790:Metoprolol