Use of PDE1A polypeptides, or nucleic acid, for identifying their specific inhibitors, which are useful for treatment and prevention of cardiac insufficiency

Use of a PDE1A polypeptide (I), or nucleic acid (II) that encodes it, in a test system for identifying inhibitors (A) of (I), suitable for treatment and/or prevention of cardiac insufficiency and the underlying cardiomyopathy. Independent claims are also included for the following: (1) use of (A), including those identified by the new method, for treatment and/or prevention of cardiac insufficiency; and (2) use of PDE1A-specific antibodies (Ab), antisense oligonucleotides and small interfering RNA for treating and/or preventing cardiac insufficiency. ACTIVITY : Cardiant; Antianginal; Hypotensive; Antiarteriosclerotic; Nephrotropic; Vasotropic. MECHANISM OF ACTION : Inhibition of PDE1A, which catalyzes hydrolysis of cGMP, resulting in reduced levels of this antihypertrophic compound in cardiomyocytes, implying that increased expression of PDE1A is responsible for cardiac hypertrophy. Compounds that inhibit PDE1A will thus have an antihypertrophic effect. The rat cardiomyocytic cell line H9C2 was treated with arginine-vasopressin (aVP) to stimulate hypertrophy, detected by increased expression of atrial natriuretic peptide (ANP) and myosin heavy chain beta -subunit (MYCHB). The relative expression in presence of 1 mu M aVP was 72 for ANP and 13 for MYCHB. When 10 mu M of the inhibitory substance X (IC50 for inhibition of PDE1A = 12 nM) was present, the corresponding figures were 18 and 3. Substance X is not identified. Die Erfindung betrifft die Verwendung von PDE1A-Inhibitoren zur Herstellung eines Arzneimittels zur Behandlung und/oder Prophylaxe von koronaren Herzkrankheiten, insbesondere stabiler und instabiler Angina pectoris, akutem Myokardinfarkt, Myokardinfarktprophylaxe, Herzinsuffizienz, sowie Bluthochdruck und den Folgen der Atherosklerose sowie Gefäßerkrankungen, Erkrankungen der Niere, insbesondere Nierenversagen, entzündlichen Erkrankungen, Erektionsstörungen und Verhinderung des plötzlichen Herztodes.