Influence of different dietary salts on the cardiovascular and renal effects of moxonidine in spontaneously hypertensive rats.
The influence of common salt (NaCl) and a novel potassium-, magnesium-, and L-lysine-enriched mineral salt on the cardiovascular and renal effects of the selective imidazoline I1-receptor agonist moxonidine was examined in spontaneously hypertensive rats (SHR). Common salt was added at the level of 6% of the dry weight of the chow, and mineral salt at a 75% higher level of 10.5% thereof to produce the same NaCl concentration of 6% as in the common salt group. During the control diet an 8-week oral treatment with moxonidine (117 mg/1000 g of the dry weight of the chow producing an approximate daily dose of 10 mg/kg), lowered blood pressure by 13 mmHg. The common salt diet alone raised blood pressure by 27 mmHg. Moxonidine lowered blood pressure by 21 mmHg during the common salt diet, but the blood pressure remained 19 mmHg higher than in the moxonidine-treated SHR receiving the control diet (P<0.05). Unlike common salt, mineral salt alone did not raise blood pressure nor did it interfere with the antihypertensive effect of moxonidine. Moxonidine showed a kidney-protective effect during the control diet measured as decreased urinary protein excretion, but it did not affect the development of left ventricular hypertrophy. Moxonidine increased plasma renin activity during the control diet and it raised the serum aldosterone level both during the control and mineral salt diets. The vascular relaxation responses of the mesenteric arterial rings to both acetylcholine (an indicator of endothelium-dependent vascular relaxation) and nitroprusside and nitroprusside (an indicator of endothelium-independent vascular relaxation) were attenuated by the common salt diet alone but maintained during the moxonidine treatment. Our findings are consistent with the concept that moxonidine is able to improve the excretion of sodium. This effect might explain the maintenance of normal vascular relaxation during a high intake of common salt. These effects may partly account for the antihypertensive effect of moxonidine.
Mervaala
E M
EM
Institute of Biomedicine, Department of Pharmacology and Toxicology, Helsinki, Finland.
Malmberg
L
L
Teräväinen
T L
TL
Lähteenmäki
T
T
Karjala
K
K
Paakkari
I
I
Pörsti
I
I
Mest
H J
HJ
Vapaatalo
H
H
Karppanen
H
H
D000450:Aldosterone / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D004326:Drinking / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D012492:Salts / Q000009:adverse effects / Q000494:pharmacology*; D017673:Sodium Chloride, Dietary / Q000009:adverse effects / Q000494:pharmacology*
D000959:Antihypertensive Agents; D001786:Blood Glucose; D007093:Imidazoles; D007328:Insulin; D012492:Salts; D017673:Sodium Chloride, Dietary; D000450:Aldosterone; C043482:moxonidine; D012083:Renin