Preventive effects of low molecular mass potassium alginate extracted from brown algae on DOCA salt-induced hypertension in rats.

Available evidence indicates that brown algae may be beneficial for the treatment of high blood pressure. Our recent study demonstrated that low molecular mass potassium alginate (L-PA), one of the major polysaccharides extracted from brown algae, decreased systolic blood pressure (SBP) in spontaneous hypertensive rats. The present study investigated the effects of L-PA on deoxycorticosterone acetate (DOCA) salt-induced hypertension in rats. Hypertension was induced by biweekly subcutaneous injections of 50mg/kg DOCA plus 1% NaCl in drinking water. The control group received saline injections. L-PA (250 or 500 mg/kg), KCl (239 mg/kg), or volume-matched solvent was administered orally once daily for 30 days. DOCA salt administration significantly increased SBP, sodium excretion, serum sodium content, circulating plasma volume (CPV), plasma atrial natriuretic peptide (ANP) content, heart and renal weight indices, and mortality and decreased plasma aldosterone (ALD) and serum potassium levels in the vehicle-treated DOCA salt group compared with the control group. However, L-PA dose-dependently normalized the above changes induced by DOCA salt, with the exception of further increasing sodium excretion, while KCl did not affect the changes caused by DOCA salt, with the exception of slightly ameliorating hypokalemia and mortality. These findings suggest that L-PA may offer a novel form of potassium supplementation with greater antihypertensive and sodium excretion actions than KCl and may likely be beneficial for the primary prevention and treatment of hypertension and its cardiovascular sequelae.

[Antihypertensive effect and pharmacokinetics of low molecular mass potassium alginate].

OBJECTIVE: To investigate the effect of low molecular weight potassium alginate (L-PA) on blood pressures in spontaneously hypertensive rats (SHRs) and its pharmacokinetics characteristics in mice. METHODS: The systolic blood pressure (SBP) was measured by tail-cuff method in conscious SHRs. Forty rats were randomly assigned to the following five groups: control, hydrochlorothiazide (HCT, 6.25 mg/kg), L-PA in low, middle or high dose groups (100, 250, 500 mg/kg). SHRs were intragastrically (i. g.) administrated once daily for 28 days. The SBP was measured once weekly during drug treatment, and 3 and 6 days after drug with drawal. KM mice were i. g. administered with 100 mg/kg (74 MBq/kg) of 3H-L-PA. Ten microl blood samples were obtained from the tail vein at 2, 5, 10, 20, 30 min and 1, 2, 4, 6, 12, 24, 48, 72, 96, 120 or 144 h after drug administration for measuring radioactivities. Pharmacokinetics parameters of the oral administration of L-PA were analysed with DAS 2.0 software. RESULTS: Twenty-one or 28 days after administration, the rats in the groups treated with HCT or L-PA at 100, 250 or 500 mg/kg had a significant decrease in SBP (P<0.01 vs control group). Three or 6 days after drug withdrawal, the antihypertensive effect of HCT disappeared (P>0.05), whereas the rats treated with 250 or 500 mg/kg L-PA still had lower SBP than the controls (P<0.01). The L-PA at a dose of 100 mg/kg also led to a significant decrease in SBP 3 days after drug withdrawal (P<0.05). The pharmacokinetics of L-PA (i. g.) was consistent with a two-compartment model, with 2.76 h of absorption half-life (t1/2, Ka), 42. 30 h of distributional half-life (t1/2alpha), 42. 31 h of elimination half-life (t1/2beta), and 36.28 h of terminal phase elimination half-life (t1/2z). CONCLUSION: Oral administration of L-PA has significant anti-hypertensive effect, which can be maintained to 6 days after drug withdrawal. The sustaining anti-hypertensive effect of L-PA is probably associated with its slow elimination in vivo.