Replacement of salt by a novel potassium- and magnesium-enriched salt alternative improves the cardiovascular effects of ramipril.
1. The influence of salt (sodium chloride; NaCl) (an additional 6% in the diet) and that of a novel sodium-reduced, potassium-, magnesium-, and L-lysine-enriched salt alternative on the cardiovascular effects of ramipril was studied in stroke-prone spontaneously hypertensive rats in a 6-week study. The intake of sodium chloride was adjusted to the same level by adding the salt alternative at a 1.75 times higher amount than regular salt. 2. Salt produced a marked rise in blood pressure and induced cardiac hypertrophy and significant mortality, while the salt alternative neither increased blood pressure nor caused any mortality and produced less cardiac hypertrophy than salt. 3. Ramipril treatment at a daily dose of 3 mg kg-1 normalized blood pressure and prevented the development of cardiac hypertrophy of rats on control diet. These effects of ramipril were blocked by the addition of salt but were only slightly attenuated by the addition of the salt alternative. The mortality in the salt group was prevented by ramipril. 4. Responses of mesenteric arterial rings in vitro were examined at the end of the study. Salt, but not the salt alternative, increased vascular contractile responses to noradrenaline. Ramipril treatment improved the arterial relaxation responses to acetylcholine and to sodium nitroprusside. The vascular relaxation enhancing effect of ramipril was blocked by salt but only slightly attenuated by the salt alternative. 5. Ramipril treatment did not significantly increase plasma renin activity in the presence or in the absence of salt supplementation. The salt alternative did not cause hyperkalaemia, either alone or in combination with ramipril treatment. 6. Both salt supplementations, irrespective of ramipril treatment, induced a six to eight fold increase in the urinary excretion of calcium. There was an expected 90 to 140% rise in the urinary excretion of magnesium and 200% rise in the urinary excretion of potassium in the salt alternative group. Salt also produced an approximately 50% increase in magnesuria.7. Our findings suggest that replacement of salt by the potassium-, magnesium- and L-lysine-enriched salt alternative improves the cardiovascular effects of ramipril. In the present study the beneficial effect was related to the increased intakes of potassium and/or magnesium and L-lysine from the salt alternative because the amount of sodium chloride was the same.
Department of Pharmacology and Toxicology, University of Helsinki, Finland.
E M
EM
Mervaala
I
I
Paakkari
J
J
Laakso
R
R
Nevala
T M
TM
Teräväinen
F
F
Fyhrquist
H
H
Vapaatalo
H
H
Karppanen
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D002561:Cerebrovascular Disorders / Q000209:etiology; D004573:Electrolytes / Q000378:metabolism; D017379:Hypertrophy, Left Ventricular / Q000209:etiology; D008274:Magnesium / Q000008:administration & dosage*; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology; D011188:Potassium / Q000008:administration & dosage*; D017257:Ramipril / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D012965:Sodium Chloride / Q000008:administration & dosage*
D004573:Electrolytes; D012965:Sodium Chloride; D008274:Magnesium; D017257:Ramipril; D011188:Potassium