Mechanisms of the therapeutic effect of astragalus membranaceus on sodium and water retention in experimental heart failure.

OBJECTIVE

To investigate the therapeutic effect of Astragali on sodium and water retention in aortocaval fistula-caused experimental congestive heart failure and its involved mechanisms.

METHODS

In aortocaval fistula-caused chronic (5 wk), heart failure rats treated with and without Astragali 1.0 g/day intraperitoneally, changes of cardiac and renal function, renal response to atrial natriuretic peptide (ANP) were examined. Dot blot analysis was used to determine the effect of Astragali on hypothalamic arginine vasopresin (AVP) mRNA expression, and mRNA expressions of aortic and renal AVP V1a receptor, renal AVP V2 receptor and aquaporin-2 (AQP2) were simultaneously detected by RT-PCR method.

RESULTS

Rats with aortocaval fistula impaired cardiac and renal functions evidenced by higher right atrial pressure (RAP), left ventricular end-diastolic pressure (LVEDP), lower + dP/dtmax of left ventricle, glomerular filtration rate (GFR), renal plasma flow (RPF), urine volume (UV), urinary sodium excretion (UNaV) and free water clearance (CH2O) compared with sham-operated control (P < 0.05). There was no change in serum sodium, hematocrit and plasma osmolality. Astragali could remarkably improve the cardiac and renal functions. Dot blot analysis demonstrated upregulated hypothalamic AVP mRNA expression in this experimental heart failure. The AVP V1a receptor mRNA level of aortic arch and renal medulla were reduced, while in renal cortex it was elevated. The mRNA expressions of AVP V2 receptor and AQP2 were increased in renal cortex while decreased in medulla. Astragali could partially or completely correct those abnormal mRNA expressions. Analysis on plasma atrial natriuretic peptide (ANP), urinary cyclic guanidino monophosphate excretion (UcGMP V), urinary cyclic guanidino monophosphate excretion/plasma atrial natriuretic peptide (UcGMP V/pANP), and further correlation and linear regression analysis between UcGMP V and plasma ANP showed that there was blunted renal response to ANP in heart failure rat, and astragali could improve the renal reaction to ANP significantly.

CONCLUSIONS

Chinese herb, astragali have therapeutic effects on sodium and water retention in aortocaval fistula-induced heart failure, the mechanisms of which might be the improvement of cardiac and renal functions, partly correction of abnormal mRNA expressions of AVP system and AQP2, and amelioration of blunted renal response to ANP.