Effect of treatment with lercanidipine on heart of Cohen-Rosenthal diabetic hypertensive rats.
The influence of treatment with the dihydropyridine-type Ca2+ antagonist lercanidipine on heart and coronary microanatomic changes was investigated in spontaneously hypertensive rats, Cohen-diabetic rats, and Cohen-Rosenthal diabetic hypertensive rats. At 12 weeks of age, animals were left untreated (control groups) or were treated for 8 weeks with an oral dose of 3 mg/kg per day of lercanidipine. Wistar-Kyoto rats were used as a normotensive reference group. In spontaneously hypertensive rats and diabetic hypertensive rats, systolic blood pressure was higher in comparison with Wistar-Kyoto rats. Augmented pressure values were decreased by lercanidipine treatment. Systolic blood pressure was slightly higher in Cohen-diabetic rats than in Wistar-Kyoto rats, and this increase was countered by treatment with lercanidipine. In spontaneously hypertensive rats, diabetic rats, and diabetic hypertensive rats, the thickness of left ventricle and cardiocyte area were increased. Focal connective tissue areas and diffuse accumulation of connective tissue were observed in the left ventricle of spontaneously hypertensive and Cohen-diabetic rats, respectively. Pharmacological treatment countered left ventricle thickening and restored cardiocyte area values in subendocardium. An increased thickness of tunica media accompanied by luminal narrowing was found in coronary artery branches of control spontaneously hypertensive and diabetic hypertensive rats. Treatment with lercanidipine countered vascular changes primarily in small-sized coronary arteries. These results indicate that hypertensive, diabetic, and diabetic hypertensive rats undergo cardiac hypertrophy and vascular changes affecting small-sized coronary arteries. Treatment with lercanidipine countered hypertension-related cardiac and coronary changes, suggesting that this dihydropyridine-type Ca2+ antagonist may improve heart and coronary structure in diabetes associated with hypertension.
Dipartimento di Scienze Farmacologiche e Medicina Sperimentale, Università di Camerino, via Scalzino 3, 62032 Camerino, Italy. francesco.amenta@unicam.it
Francesco
F
Amenta
Edna
E
Peleg
Daniele
D
Tomassoni
Maurizio
M
Sabbatini
Talma
T
Rosenthal
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004095:Dihydropyridines / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C060343:lercanidipine