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L-007 METOPROLOL ANTIHYPERTENSIVE EFFECT IN SPONTANEOUSLY HYPERTENSIVE RATS WITH RAAV1 MEDIATED BETA1-ADRENERGIC RECEPTOR GENE OVEREXPRESSION

Background To construct the recombinant adeno-associated virus in which beta1-AR is over expressed. Investigated the effects of over expressing beta1-AR on metoprolol antihypertension of SHRs. Methods Randomly taking out 6 spontaneously hypertensive rats (SHRs) as rAAV1/CMV-EGFP group, others were randomly divided into 3 groups: rAAV1/CMV-Adrb1 + metoprolol Group (n = 6), surgical + metoprolol Group (n = 6) and surgical + saline Group (n = 6). All of them were measured blood pressure (BP) by weekly and adjusted the dose of metoprolol according to their weight. Four weeks later SHRs were killed. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Real-time RT-PCR were used to assay mRNA expression of beta1-AR gene, protein expression of beta1-AR were analyzed by Immunohistochemistry and Western blot. Results Expression of beta1-AR gene in each group: RT-PCR and Real-time RT-PCR results showed that rAAV1/CMV-Adrb1 injection significantly increase beta1-AR mRNA expression in myocardial tissue of SHRs (0.587 ± 0.132 vs. 0.212 ± 0.075, P < 0.05), Immunohistochemistry and Western blot results demonstrated that rAAV1/CMV-Adrb1 injection could significantly increase the expression of beta1-AR protein in myocardial tissue of SHRs (0.545 ± 0.119 vs. 0.421 ± 0.136, P < 0.05). Antihypertensive effects of each group: After 4 weeks of intervention, Systolic BP were significantly lower in the rAAV1/CMV-Adrb1+metoprolol group and the surgical + metoprolol group than that in the saline group (176.2 ± 8.5mmHg vs. 182.5 ± 4.5mmHg vs. 198.7 ± 7.0 mmHg, P < 0.05); The reduction of Systolic BP was significantly higher than in the rAAV1/CMV-Adrb1+metoprolol group than that in the sham group (27.8 ± 8.5mmHg vs. 16.8 ± 2.5mmHg, P < 0.05). Conclusion The rAAV1/CMV-Adrb1 can significantly increase the expression of beta1-AR in myocardial of SHRs. The SHRs whose beta1-AR gene is over expressed may have better antihypertensive response to metoprolol and it may be one of the reason for influencing the individual antihypertensive response of metoprolol.