Control of cardiomyocyte gene expression as drug target.
Pressure overload of the heart is associated with a perturbed gene expression of the cardiomyocyte leading to an impaired pump function. The ensuing neuro-endocrine activation results in disordered influences of angiotensin II and catecholamines on gene expression. To assess whether angiotensin II type 1 receptor inhibition can also counteract a raised sympathetic nervous system activity, spontaneously hypertensive rats fed a hypercaloric diet were treated with eprosartan (daily 90 mg/kg body wt) and cardiovascular parameters were monitored with implanted radiotelemetry pressure transducers. Both, blood pressure and heart rate were increased (p < 0.05) by the hypercaloric diet. Although eprosartan reduced (p < 0.05) the raised systolic and diastolic blood pressure, the diet-induced rise in heart rate was blunted only partially. In addition to drugs interfering with the enhanced catecholamine influence, compounds should be considered that selectively affect cardiomyocyte gene expression via 'metabolic' signals.
Rupp
H
H
Department of Internal Medicine and Cardiology, Philipps University of Marburg, Germany.
Benkel
M
M
Maisch
B
B
D000179:Acrylates / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000737:chemistry / Q000235:genetics*; D002395:Catecholamines / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006333:Heart Failure / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000235:genetics*; D051381:Rats; D011918:Rats, Inbred SHR; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000235:genetics*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013876:Thiophenes
D000179:Acrylates; D000959:Antihypertensive Agents; D002395:Catecholamines; D007093:Imidazoles; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D013876:Thiophenes; C068373:eprosartan; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D018995:Myosin Heavy Chains; D000252:Calcium-Transporting ATPases