Abstract: AIM: To investigate the effects of β₁-adrenergic receptor mRNA antisense oligodeoxynucleotide (β₁-AS-ODN) mediated by the cationic liposomes (DOT-AP/DOPE) on the hemodynamics and cardiac hypertrophy of renal hypertensive rats.METHODS: The two-kidney and one-clip (2K1C) rat models were established and divided into five groups: the sham-operated group, the 2K1C group, the 2K1C +inverted ODN (IN-ODN ) group, the 2K1C + antisense oligodeoxynucleotide (ASODN) group and the 2K1C +carvedilol group. Single intravenous injection of ODN 0. 5 mg·kg^-1 was given after four weeks of operation and carvedilol 10 mg·kg^-1 ·d^-1 was administrated for 4 weeks. Blood pressure was measured regularly. Hemodynamic parameters, left ventricular weight index (LVWI) and plasma endothelin-1(ET-1) concentration were measured after eight weeks of operation The linear correlation between LVWI and ET-1 were analyzed.RESULTS: Compared with the IN-ODN group, β₁-AS-ODN significantly decreased SBP (P<0.01), increased±d_p dt_max (P<0.01), and had an obvious suppressive effect on LVSP (P<0. 05 ), LVEDP (P<0.01), LVWI (P<0. 05) and ET-1(P<0.01). No significant difference was found between the AS-ODN group and the carvedilol group. In addition, LVWI positively correlated with ET-1 (r =0.749, P<0.01).CONCLUSION: β₁-AS-ODN mediated by the cationic liposomes has an effective long-term antihypertensive effect with single intravenous injection. It can also improve the hemodynamics and attenuate cardiac hypertrophy. These effects may relate to their effect of decreasing the concentration of plasma ET-1.

Key words: beta-1 adrenergic receptor, antisense oligodeoxynucleotide, renal hypertension, hemodynamics, cardiac hypertrophy