Antihypertensive effect of trandolapril and verapamil in rats with induced hypertension.
The antihypertensive effect of long-term treatment (6 months) with placebo (as control), verapamil, trandolapril, and their combination (verapamil plus trandolapril) was investigated in Wistar rats rendered hypertensive by extensive renal mass ablation, as a model lacking genetic hypertensive determinants. Arterial pressure was monitored during treatment and at the end, aortic structure and functionality were investigated. Trandolapril and the combination prevented the increase in pressure observed in the control group after renal handicap, whereas verapamil was much less effective. Trandolapril and the combination were similarly effective, whereas verapamil was ineffective, or even deleterious, at reducing aortic lamina media hypertrophy, the wall-to-lumen ratio, lamina media cross-sectional area, potassium chloride-induced contraction, and at increasing acetylcholine relaxation. The response to noradrenaline decreased in the trandolapril group, increased in the verapamil group, and remained unmodified in the association group. In conclusion, treatment with trandolapril exerts beneficial antihypertensive actions in this model of induced hypertension, showing continuous control of blood pressure and prevention of structural and functional alteration of the aorta. Verapamil exerts weak control of arterial pressure and produces, if any, deleterious effects on the structure and function of the aorta. These negative effects of verapamil are overcome by coadministration of trandolapril.
López-Hernández
F J
FJ
Department of Fisiología y Farmacología, Facultad de Medicina, Universidad de Salamanca, Spain.
Carrón
R
R
Montero
M J
MJ
Flores
O
O
López-Novoa
J M
JM
Arévalo
M A
MA
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D006973:Hypertension / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D066298:In Vitro Techniques; D007211:Indoles / Q000627:therapeutic use*; D007238:Infarction / Q000150:complications / Q000473:pathology; D007668:Kidney / Q000098:blood supply / Q000473:pathology; D008026:Ligation; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D007211:Indoles; C052035:trandolapril; D014700:Verapamil