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 congest ive heart failure and its involved mechanisms. Methods In aortocaval f istula-caused chronic (5 wk) heart failure rats treated with and witho ut Astragali 1.0 g/day intraperitoneally, changes of cardiac and renal function, renal response to atrial natriuretic peptide (ANP) were exa mined. Dot blot analysis was used to determine the effect of Astragali -on hypothalamic arginine vasopresin (AVP) mRNA expression, and mRNA e xpressions of aortic and renal AVP V(1)a receptor, renal AVP V-2 recep tor and aquaporin-2 (AQP2) were simultaneously detected by RT-PCR meth od. Results Rats with aortocaval fistula impaired cardiac and renal fu nctions evidenced by higher right atrial pressure (RAP), left ventricu lar end-diastolic pressure (LVEDP), lower + dP/dt(max) of left ventric le, glomerular filtration rate (GFR), renal plasma flow (RPF), urine v olume (UV), urinary sodium excretion (UNaV) and free water clearance ( C-H2O) compared with sham-operated control (P<0.05). There was no chan ge 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 expe rimental heart failure. The AVP V(1)a receptor mRNA level of aortic ar ch and renal medulla were reduced, while in renal cortex it was elevat ed. The mRNA expressions of AVP V-2 receptor and AQP2 were increased i n renal cortex while decreased in medulla. Astragali could partially o r completely correct those abnormal mRNA expressions. Analysis on plas ma atrial natriuretic peptide (ANP), urinary cyclic guanidino monophos phate excretion (U-cGMP V), urinary cyclic guanidino monophosphate exc retion /plasma atrial natriuretic peptide (U-cGMP V / pANP), and furth er correlation and linear regression analysis between U-cGMP V and pla sma ANP showed that there was blunted renal response to ANP in heart f ailure rat, and astragali could improve the renal reaction to ANP sign ificantly. Conclusion Chinese herb, astragali have therapeutic effects on sodium and water retention in aortocaval fistula-induced heart fai lure, 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.