Effects Of Antisense Oligodeoxynucletide Of β₁ Adrenergic Acceptor On Renal Hypertension Rats

Backgroud The sympathetic nervous system plays a crucial role in the cardiovascular disease such as hypertension and cardiac arrhythmia. Through the inhibition of β -adrenergic receptors in heart and kidney, β -blockers lower high pressure via the reduced response to the sympathetic nervous systems. But despite great success with traditional therapy , there are still many patients with poorly controlled high blood pressure and target organs dysfunction due to side effects including central nervous system reaction (eg, sleep disturbance, depression, impotence, dizziness, and fatigue) and β₂-adrenergic antagonistic activity (eg, increase in peripheral vascular resistance, worsening of asthma symptoms) . In addition, because of their short half-life (3 to 10 hours) , β-blockers must be taken daily to be effective. Antisense oligodexynucleotide has been well used as a pharmacological tool to inhibit the effect of corresponding protein. Antisense therapy studies were carried out as the treatment for HIV, hypertension, cardiovascular disease , Leukenia. Zaugg et al had successfully proved that antisense Inhibition of β₁-adrenergic receptor mRNA in a single dose produces a profound and prolonged reduction in high blood pressure in spontaneously hypertensive rats. Cardiac hyperthophy is an independent risk factor for cardiac morbility. Apoptosis plays a role in the regulation of cell mass and architecture in many tissues including heart. Increased apoptosis has been reported in the heart of rats with spontaneous hypertension and cardiac hypertrophy.Objective To explore the role of antisense oligodeoxynucletide of β1-adrenergic receptor for anti-hypertension effect and anti-apoptosis effect.Methods Establish the model of 2K1C renal hypertension. They were stochastically divided into 4 groups, 6 rats each. A group were injected with antisense oligodeoxynucletide of 0.5mg · kg^-1. B group were injected with inverted antisense oligodeoxynucletide of 0.5mg ·kg^-1. C group were fed with carvedilol of 10mg ·Kg^-1 ·d^-1. The apoptosis were detected by Tunel. The content of iNOS were detected by sp.Results It was shown that blood pressure droped markedly (P<0.01) ,in groups which were injected with antisense oligodeoxynucletide and fed with carvedilol. The left ventricular weight/body weight decreased marked, (P<0.01) ,in groups which were injected with antisense oligodeoxynucletide and fed with carvedilol. (P<0.01) It was shown apoptosis of cardiomyocyte of 2K1C control group and invereted antisense oligodeoxynucletide group was higher than antisense oligodeoxynucletide group (P< 0.01) . The content of iNOS were higher in 2K1C control group and inverted antisense oligodeoxynucletide group than antisense oligodeoxynucletide group (P<0.01) .Conclution Antisense oligodeoxynucletide have the effect of depressing the blood pressure. What's more, both antisense oligodeoxynucletide and carvedilol have restrained apoptosis of cardiomyocyte and staved the heart failure. The increased apoptosis of cardiomyocytes may be the pathophysiological mechanism of cardiovascular remodeling.