Disclosed are antisense oligonucleotide, polynucleotide, and peptide
nucleic acid compounds that specifically bind to mammalian mRNA encoding a
.beta..sub.1 -adrenoceptor polypeptide and that are useful in the control
and/or treatment of cardiac dysfunction, hypertension, hypertrophy,
myocardial ischemia, and other cardiovascular diseases in an affected
mammal, and preferably, in a human subject. The antisense compounds
disclosed herein, and pharmaceutical formulations thereof, provide
sustained control of .beta..sub.1 -adrenoceptor expression over prolonged
periods, and achieve therapeutic effects from as little as a single dose.
Administration of these antisense compositions to approved animal models
resulted in a decrease in blood pressure, but no significant change in
heart rate. Use of such antisense compositions in the reduction of
.beta..sub.1 -adrenoceptor polypeptides in a host cell expressing
.beta..sub.1 -adrenoceptor-specific mRNA, and in the preparation of
medicaments for treating human and animal diseases, and in particular,
hypertension and other cardiac dysfunction is also disclosed.