The combination of atenolol and amlodipine is better than their monotherapy for preventing end-organ damage in different types of hypertension in rats.
Combinations therapy is often used in hypertensive patients whether combination therapy is necessary for preventing end-organ damage is not known. The objective of this study was to determine in four different hypertensive animal models the necessity of adding the calcium channel blocker amlodipine to therapy with the ss-blocker atenolol to modulate end-organ damage. Spontaneously hypertensive rats, DOCA-salt hypertensive rats, two-kidney, one-clip renovascular hypertensive rats and Lyon genetically hypertensive rats were used to study this objective. These animal models have different sensitivities to atenolol and amlodipine. The dosages of therapy employed were 10 mg/kg atenolol alone, 1 mg/kg amlodipine, 10 mg atenolol + 1 mg/kg amlodipine and 5 mg/kg atenolol+0.5 mg/kg amlodipine. BP was continuously recorded in all animals. After determination of baroreflex sensitivity, rats were sacrificed for end-organ damage evaluation. The combination of amlodipine and atenolol had a synergistic inhibitory effect on blood pressure and blood pressure variability, and end-organ damage as compared with monotherapy with atenolol or amlodipine in all animal models. Baroreflex sensitivity also improved with the combination therapy more than with monotherapy. In conclusion, atenolol and amlodipine combination exerts a superior effect on blood pressure, blood pressure variability, baroreflex sensitivity and end-organ damage. The superior effect of the combination was observed in all four models of hypertension.
Han
Ping
P
Department of Pharmacology, Second Military Medical University, Shanghai, China.
Shen
Fu-Ming
FM
Xie
He-Hui
HH
Chen
Yuan-Yuan
YY
Miao
Chao-Yu
CY
Mehta
Jawahar L
JL
Sassard
Jean
J
Su
Ding-Feng
DF
D017311:Amlodipine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004359:Drug Therapy, Combination; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009928:Organ Specificity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis; D013997:Time Factors
D017311:Amlodipine; D001262:Atenolol